This morning, Megan A. Adams (a GI & Hepatology News Associate Editor and a Michigan faculty member) and I held an hour-long video conference with all of our Michigan GI fellows. Our four third-year fellows talked about their job search and employment plans for July. Three will join academic centers (UNC, University of Wisconsin, Henry Ford) and one will enter private practice (Atlanta Gastroenterology). I was glad to hear that all had been reassured that their positions were secure despite the COVID-19 impact. As I speak with colleagues across the country, all (whether health system physicians, academic faculty, or community gastroenterologists) are experiencing the financial, emotional, and operational effects of this pandemic. This is an experience that will define our professional careers.

As one of three chief clinical officers at Michigan Medicine, I am part of a four-person team that leads the faculty medical group and the ambulatory portion of our health system. Each of our segments (ambulatory, adult hospital, children’s hospital, and medical school) have targets for sustained cost reductions that total $400 million and Michigan Medicine (as published in the news) plans to reduce our workforce (nonfaculty) by 1,400. We have a hiring freeze, leaders are taking salary reductions, and we have instituted other painful, cost-saving measures. The physician leaders we hired just 12 months ago to oversee a new faculty group structure were thrust into a firestorm. Department chairs, division chiefs, nursing and administrative leaders all are having to make heart-wrenching cost-cutting decisions. Together, we have to make individual reductions in force or retain decisions about people we work with daily. This emotional toll will never truly heal for anyone involved.

There will be little time to recover. We are scrambling to reopen safely, with a planned process. We have a backlog of 12,000 surgeries and 8,000 endoscopy procedures that have been deferred. Eight-hundred children are behind in their well-child medical care, frightened patients are sitting home with critical aortic stenosis, dangerous hypertension, growing cancers, and other urgent medical needs. Private practices are facing the same issues, financial pressures, and emotional toll.

Anna Quindlen once said, “Grief is a whisper in the world, but a clamor within.” Recognize the toll this is taking and don’t be alone with your grief.

John I. Allen, MD, MBA, AGAF
Editor in Chief

This morning, Megan A. Adams (a GI & Hepatology News Associate Editor and a Michigan faculty member) and I held an hour-long video conference with all of our Michigan GI fellows. Our four third-year fellows talked about their job search and employment plans for July. Three will join academic centers (UNC, University of Wisconsin, Henry Ford) and one will enter private practice (Atlanta Gastroenterology). I was glad to hear that all had been reassured that their positions were secure despite the COVID-19 impact. As I speak with colleagues across the country, all (whether health system physicians, academic faculty, or community gastroenterologists) are experiencing the financial, emotional, and operational effects of this pandemic. This is an experience that will define our professional careers.

As one of three chief clinical officers at Michigan Medicine, I am part of a four-person team that leads the faculty medical group and the ambulatory portion of our health system. Each of our segments (ambulatory, adult hospital, children’s hospital, and medical school) have targets for sustained cost reductions that total $400 million and Michigan Medicine (as published in the news) plans to reduce our workforce (nonfaculty) by 1,400. We have a hiring freeze, leaders are taking salary reductions, and we have instituted other painful, cost-saving measures. The physician leaders we hired just 12 months ago to oversee a new faculty group structure were thrust into a firestorm. Department chairs, division chiefs, nursing and administrative leaders all are having to make heart-wrenching cost-cutting decisions. Together, we have to make individual reductions in force or retain decisions about people we work with daily. This emotional toll will never truly heal for anyone involved.

There will be little time to recover. We are scrambling to reopen safely, with a planned process. We have a backlog of 12,000 surgeries and 8,000 endoscopy procedures that have been deferred. Eight-hundred children are behind in their well-child medical care, frightened patients are sitting home with critical aortic stenosis, dangerous hypertension, growing cancers, and other urgent medical needs. Private practices are facing the same issues, financial pressures, and emotional toll.

Anna Quindlen once said, “Grief is a whisper in the world, but a clamor within.” Recognize the toll this is taking and don’t be alone with your grief.

John I. Allen, MD, MBA, AGAF
Editor in Chief

This morning, Megan A. Adams (a GI & Hepatology News Associate Editor and a Michigan faculty member) and I held an hour-long video conference with all of our Michigan GI fellows. Our four third-year fellows talked about their job search and employment plans for July. Three will join academic centers (UNC, University of Wisconsin, Henry Ford) and one will enter private practice (Atlanta Gastroenterology). I was glad to hear that all had been reassured that their positions were secure despite the COVID-19 impact. As I speak with colleagues across the country, all (whether health system physicians, academic faculty, or community gastroenterologists) are experiencing the financial, emotional, and operational effects of this pandemic. This is an experience that will define our professional careers.

As one of three chief clinical officers at Michigan Medicine, I am part of a four-person team that leads the faculty medical group and the ambulatory portion of our health system. Each of our segments (ambulatory, adult hospital, children’s hospital, and medical school) have targets for sustained cost reductions that total $400 million and Michigan Medicine (as published in the news) plans to reduce our workforce (nonfaculty) by 1,400. We have a hiring freeze, leaders are taking salary reductions, and we have instituted other painful, cost-saving measures. The physician leaders we hired just 12 months ago to oversee a new faculty group structure were thrust into a firestorm. Department chairs, division chiefs, nursing and administrative leaders all are having to make heart-wrenching cost-cutting decisions. Together, we have to make individual reductions in force or retain decisions about people we work with daily. This emotional toll will never truly heal for anyone involved.

There will be little time to recover. We are scrambling to reopen safely, with a planned process. We have a backlog of 12,000 surgeries and 8,000 endoscopy procedures that have been deferred. Eight-hundred children are behind in their well-child medical care, frightened patients are sitting home with critical aortic stenosis, dangerous hypertension, growing cancers, and other urgent medical needs. Private practices are facing the same issues, financial pressures, and emotional toll.

Anna Quindlen once said, “Grief is a whisper in the world, but a clamor within.” Recognize the toll this is taking and don’t be alone with your grief.

John I. Allen, MD, MBA, AGAF
Editor in Chief

Francisco Alvarez, MD
Associate Chief, Regional Pediatric Hospitalist Programs
Lucile Packard Children’s Hospital
Clinical Associate Professor
Stanford University School of Medicine
Stanford, CA
Fever of Unknown Origin

Brian Alverson, MD
Director, Division of Pediatric Hospital Medicine
Hasbro Children’s Hospital
Professor of Pediatrics
Alpert School of Medicine, Brown University
Providence, RI
Pneumonia

Eric Balighian, MD
Director, Pediatric Emergency Department
St. Agnes Hospital
Asistant Professor, Department of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD
Acute Abdominal Pain and Acute Abdomen

Julia Beauchamp-Walters, MD
Medical Director, Helen Bernardy Center for Medically Fragile Children
Medical Director, Home Care
Co-Medical Director, Emergency Transport Program
Rady Children’s Hospital
Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Feeding Tubes
Pediatric Interfacility Transport

Eric Biondi, MD, MS
Director, Pediatric Hospital Medicine Division
Johns Hopkins Children’s Center
Associate Professor of Pediatrics
The Johns Hopkins Hospital University School of Medicine
Baltimore, MD
Neonatal Fever

Rebecca Blankenberg, MD, MPH
Associate Chair of Education
Stanford Lucile Packard Children’s Hospital
Clinical Associate Professor of Pediatrics and Emergency Medicine
Stanford University School of Medicine
Stanford, CA
Education

Colin Bridgeman, MD
Penn State Children’s Hospital
Assistant Professor of Pediatrics
Division of General Inpatient Pediatrics
Penn State College of Medicine
Hershey, PA
Head and Neck Disorders

Jeffrey Brown, MD, MPH, CAP, FAAP
Texas Newborn Services/Pediatrix Medical Group
Clinical Professor of Pediatrics
University of Colorado School of Medicine
Fort Worth, TX
Business Practices

April O. Buchanan, MD
Associate Dean for Curriculum
Prisma Health Children’s Hospital at Greenville
Associate Professor of Clinical Pediatrics
University of South Carolina School of Medicine
Greenville, SC
Sepsis and Shock

Douglas Carlson, MD
Medical Director
HSHS St. John’s Children’s Hospital
Professor and Chair of Pediatrics
Southern Illinois University School of Medicine
Springfield, MO
Procedural Sedation

Pearl Chang, MD
Seattle Children’s Hospital
Assistant Professor
Department of Pediatrics, University of Washington
Seattle, WA
Neonatal Jaundice

Eric Coon, MD, MS
Co-Director, Pediatric Hospital Medicine Fellowship
Primary Children’s Medical Center
Assistant Professor of Pediatrics
University of Utah Health Science
Salt Lake City, UT
Research

Yasmeen N. Daud, MD
St. Louis Children’s Hospital
Associate Professor of Pediatrics
Washington University School of Medicine
St. Louise, MO
Oxygen Delivery and Airway Management

Sarah Denniston, MD, FAAP
Fellowship Director, Pediatric Hospital Medicine
The Floating Hospital for Children at Tufts Medical Center
Assistant Professor of Pediatrics
Tufts University School of Medicine
Associate DIO for Quality and Safety
Tufts Medical Center
Boston, MA
Peri-procedural Care

Craig C. DeWolfe, MD, MEd, FAAP
Children’s National Health System
Director of Medical Student Education in Pediatrics
Associate Professor of Pediatrics,
George Washington University School of Medicine
Washington, DC
Brief Resolved Unexplained Event

Stephanie Anne Deutsch, MD, MS, FAAP
Section Chief, Child Abuse Pediatrics
Nemours/Alfred I. duPont Hospital for Children
Co-medical Director, CARE (Children at Risk Evaluation) Program
Assistant Clinical Professor of Pediatrics
Sidney Kimmel Medical College at Thomas Jefferson University
Wilmington, Delaware
Child Abuse and Neglect

Ami Doshi, MD
Medical Director, Inpatient Palliative Care Program
Rady Children’s Hospital San Diego
Clinical Associate Professor of Pediatrics
University of California San Diego School of Medicine
San Diego, CA
Palliative Care and Hospice

Erin Fisher, MD, FAAP, MHM
Medical Director, Quality Improvement
Rady Children’s Hospital San Diego
Professor of Clinical Pediatrics
Director, Pediatric Quality and Safety Graduate Medical Education
Fellowship Director and Division Director, Pediatric Hospital Medicine
University of California San Diego School of Medicine
San Diego, CA
Quality Improvement

Sandra Gage, MD, PhD, FAAP, SFHM
Associate Division Chief and Associate Fellowship Director
Division of Hospital Medicine
Phoenix Children’s Hospital
Clinical Associate Professor
University of Arizona College of Medicine – Phoenix
Department of Child Health
Phoenix, AZ
Acute Gastroenteritis
Gastrointestinal and Digestive Disorders

Mary Pat Gallagher, MD
Director, Pediatric Diabetes Center
Division of Pediatric Endocrinology, Hassenfeld Children’s Hospital
Assistant Professor
Department of Pediatrics
NYU Langone
New York, NY
Diabetes Mellitus

Amrit Gill, MD
Cleveland Clinic Children’s Hospital
Clinical Assistant Professor of Pediatrics
Case Western Reserve University School of Medicine
Cleveland, OH
Patient Safety

Veena Goel Jones, MD, FAAP
Medical Director, Digital Patient Experience, Sutter Health
Sutter Palo Alto Medical Foundation
Palo Alto, CA
Health Information Technology

Jeffrey Grill, MD
Vice Chair, Community Relations and Outreach
Chief, Division of Pediatric Hospital Medicine
Director, Just for Kids Hospitalist Service
Norton Children’s Hospital
Professor, Department of Pediatrics
University of Louisville School of Medicine
Louisville, KY
Constipation

Arun Gupta, MD
Director, Neonatal Hospitalist Program
Lucile Packard Children’s Hospital Stanford
Clinical Associate Professor, Pediatrics
Stanford University School of Medicine
Stanford, CA
Newborn Care and Delivery Room Management

Brian F Herbst Jr, MD
Medical Director, Hospital Medicine Adult Care
Division of Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Assistant Professor of Internal Medicine and Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Adolescent and Young Adult Medicine

Daniel Hershey, MD, SFHM
Rady Children’s Hospital
Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Non-invasive Monitoring

Kim Hoang, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Stanford University School of Medicine
Stanford, CA
Education

Alison Volpe Holmes, MD, MPH
Children’s Hospital at Dartmouth-Hitchcock
Associate Dean for Student Affairs, Career Advising
Vice-Chair for Education, Department of Pediatrics
Associate Professor of Pediatrics and of The Dartmouth Institute
Geisel School of Medicine at Dartmouth
Hanover, NH
Neonatal Abstinence Syndrome/Neonatal Opioid Withdrawal Syndrome

Akshata Hopkins, MD, FAAP, FHM
Director, Pediatric Residency Program
Johns Hopkins All Children’s Hospital
Assistant Professor of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL
High Value Care

Yemisi Jones, MD, FAAP, FHM
Co-Medical Director, Continuing Medical Education
Co-Director Liberty Simulation Education
Cincinnati Children’s Hospital Medical Center
Assistant Professor of Clinical Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Intravenous Access and Phlebotomy

Alisa Khan, MD, MPH
Health Services Researcher
Division of General Pediatrics, Boston Children’s Hospital
Clinical Instructor in Pediatrics
Harvard Medical School
Boston, MA
Family Centered Care

Vivian Lee, MD
Children’s Hospital Los Angeles
Clinical Assistant Professor of Pediatrics
University of Southern California Keck School of Medicine
Los Angeles, CA
Altered Mental Status

Su-Ting T. Li, MD, MPH
Associate Vice Chair of Education
Pediatric Residency Program Director
University of California Davis Children’s Hospital
Professor of Pediatrics
University of California, Davis
Sacramento, CA
Skin and Soft Tissue Infections

Patricia S. Lye, MD, MEd, FAAP
Children’s Hospital of Wisconsin
Professor of Pediatrics, Retired
Medical College of Wisconsin
Milwaukee, WI
Handoffs and Transitions of Care

Tamara Maginot, PhD
Pediatric Psychologist
Program Director, Medical Behavioral Unit
Rady Children’s Hospital San Diego
Assistant Professor, Department of Psychiatry
UC San Diego Eating Disorders Center for Treatment and Research Behavioral Medicine
San Diego, CA
Chronic Behavioral and Psychiatric Conditions

Christopher Maloney, MD, PhD, FAAP
Chief Medical Officer and Senior Vice President
Children’s Hospital & Medical Center
Professor of Pediatrics and Pediatric Critical Care
Department of Pediatrics
University of Nebraska Medical Center College of Medicine
Omaha, NE 
Pediatric Advanced Life Support

Jennifer Maniscalco, MD, MPH, MAcM, FAAP
Designated Institutional Official
Johns Hopkins All Children’s Hospital
Assistant Professor
Department of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL
Failure to Thrive

Elizabeth Mannino Avila, MD
Rady Children’s Hospital
Assistant Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Kawasaki Disease

Alison Markowsky, MD, MSHS, FAAP
Medical Director
Children’s National Pediatric Hospitalist Program at Mary Washington Healthcare
Children’s National Health System
Assistant Professor of Pediatrics
The George Washington University School of Medicine & Health Sciences
Washington, DC
Newborn Care and Delivery Room Management

Michelle Marks, DO, FAAP, SFHM
Chair, Pediatric Hospital Medicine
Cleveland Clinic Children’s Hospital
Clinical Associate Professor
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University
Cleveland, OH
Nutrition

Armand H. Matheny Antommaria, MD, PhD, FAAP
Lee Ault Carter Chair Pediatric Ethics and Pediatric Hospitalist
Cincinnati Children’s Hospital
Associate Professor of Clinical-Affiliated
University of Cincinnati School of Medicine
Cincinnati, OH
Ethics

Erich Maul, MD
Division Chief, Hospital Medicine
Medical Director, Acute Care and Progressive Care
Kentucky Children’s Hospital
Professor of Pediatrics
University of Kentucky School of Medicine
Lexington, KY
Electrocardiogram Interpretation

Rusty McCulloh, MD
Chief, Division of Hospital Medicine
Children’s Hospital & Medical Center
Associate Professor, Division of Hospital Medicine
University of Nebraska College of Medicine
Omaha, NE
Infection Control and Antimicrobial Stewardship

Anjna Melwani, MD
Director, Preoperative Care Clinic
Children’s National Medical Center
Associate Professor of Pediatrics
George Washington University School of Medicine and Health Sciences
Washington, DC
Consultation and Co-management

Christopher Miller, MD
Pediatric Allergist
Children’s Mercy Hospitals and Clinics
Assistant Professor of Pediatrics
Section of Allergy and Immunology
University of Missouri-Kansas City School of Medicine
Kansas City, MO
Asthma

Vineeta Mittal, MD, MBA
Imm. Past President of the Medical/Dental Staff
Children’s Medical Center
Associate Professor of Pediatrics
Director of Pediatric Hospital Medicine
Department of Pediatrics
UT Southwestern Medical Center & Children’s Health System Dallas
Dallas, TX
Acute Respiratory Failure

Beth Natt, MD, MPH, FAAP, SFHM
Director, Pediatric Hospital Medicine, Regional Programs
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Farmington, CT
Bladder Catheterization and Interpretation of Urinalysis

Jennifer O’Toole, MD, MEd, FAAP, SFHM
Program Director, Internal Medicine – Pediatrics Residency
Director of Education, Division of Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Associate Professor of Pediatrics and Internal Medicine
University of Cincinnati College of Medicine
Cincinnati, OH
Adolescent and Young Adult Medicine

Mary Ottolini, MD, MPH, MEd, FAAP
George W. Hallett Chair of Pediatrics
Barbara Bush Children’s Hospital at Maine Medical Center
Professor of Pediatrics
Tufts University School of Medicine
Portland, ME
Fluid and Electrolyte Management

Jack Percelay, MD, MPH, FAAP, MHM
Stanford Lucile Packard Children’s Hospital
Clinical Associate Professor of Pediatrics
Stanford University School of Medicine
Stanford, CA
Advocacy
Seizures

Shannon Phillips, MD, MPH
Chief Patient Safety and Experience Officer
Primary Children’s Medical Center
Intermountain Healthcare, Inc.
Adjunct Associate Professor of Pediatrics
University of Utah Health Sciences
Salt Lake City, UT
Patient Safety

David Pressel, MD, PhD, FAAP, FHM
Medical Director, Pediatric Hospitalist Program
Capital Health Medical Center- Hopewell
Pennington, NJ
Acute Behavioral and Psychiatric Conditions
Child Abuse and Neglect

Ricardo Quinonez, MD, FAAP
Chief, Pediatric Hospital Medicine
Texas Children’s Hospital
Associate Professor of Pediatrics
Baylor College of Medicine
Houston, TX
High Value Care

Shawn Ralston, MA, MD, MS
Johns Hopkins Children’s Center
Editor, Hospital Pediatrics, American Academy of Pediatrics
Associate Professor of Pediatrics
Division of Pediatric Quality and Safety
The Johns Hopkins Hospital University School of Medicine
Baltimore, MD
Evidence Based Medicine

David I. Rappaport, MD, FAAP, FHM
Associate Residency Program Director
Division of General Pediatrics
Nemours/AI duPont Hospital for Children
Wilmington, DE
Associate Professor of Pediatrics
Sidney Kimmel Medical College at Jefferson
Philadelphia, PA
Consultation and Co-management

Daniel Rauch, MD, FAAP, SFHM
Chief, Pediatric Hospital Medicine
The Floating Hospital for Children at Tufts Medical Center.
Professor of Pediatrics
Tufts University School of Medicine
Boston, MA
Preventive Care Services

Kyung (Kay) Rhee, MD, MSc, MA
Director of Research, Division of Pediatric Hospital Medicine
Medical Director, Medical Behavioral Unit
Rady Children’s Hospital San Diego
Professor of Clinical Pediatrics
Department of Pediatrics, Division of General Academic Pediatrics, Developmental Pediatrics, and Center for Community Health
University of San Diego School of Medicine
San Diego, CA
Chronic Behavioral and Psychiatric Conditions

Jeffrey Riese, MD
Associate Pediatric Residency Program Director
Hasbro Children’s Hospital
Associate Professor of Pediatrics
Warren Alpert School of Medicine at Brown University
Providence, RI
Neonatal Fever

Ken Roberts, MD, FAAP
Professor Emeritus of Pediatrics
University of North Carolina School of Medicine
Chapel Hill, NC
Urinary Tract Infections

Amanda Rogers, MD
Associate Pediatric Residency Program Director
Children’s Hospital of Wisconsin
Assistant Professor, Section of Hospital Medicine
Medical College of Wisconsin
Milwaukee, WI
Lumbar Puncture

Rebecca E. Rosenberg, MD, MPH
Chief, Section of Hospital Medicine, Division of General Pediatrics
Hassenfeld Children’s Hospital at NYU Langone Health
Associate Professor of Pediatrics
NYU School of Medicine
New York, NY
Peri-procedural Care

Michael Ruhlen, MD, MHCM, FHM, FACHE
Vice President, Division of Medical Education
Vice Chair, RRC ACGME
Atrium Health System
Charlotte, NC
Legal Issues and Risk Management

Christopher J. Russell, MD, MS, FAAP
Research Director, Division of Hospital Medicine
Children’s Hospital Los Angeles
Assistant Professor of Clinical Pediatrics
Keck School of Medicine, University of Southern California
Los Angeles, CA
Child with Medical Complexity

Christopher Russo, MD
Director of Pediatrics
Central Lynchburg General Hospital
Assistant Professor of Pediatrics
Liberty University College of Osteopathic Medicine
Lynchburg, VA
Advocacy

Klint M. Schwenk, MD, MBA, FAAP, FHM
Associate Division Chief, Pediatric Hospital Medicine
Norton Children’s Hospital
Associate Professor of Pediatrics
University of Louisville
Louisville, KY
Acute Gastroenteritis
Gastrointestinal and Digestive Disorders

Anand Sekaran, MD, FAAP
Associate Chair of Pediatrics, Clinical Affairs
Division Chief, Hospital Medicine
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Hartford, CT
Diagnostic Imaging

Kristin A. Shadman, MD, FAAP
American Family Children’s Hospital
Associate Professor of Pediatrics
Division of Hospital Medicine
University of Wisconsin School of Medicine and Public Health
Madison, WI
Oxygen Delivery and Airway Management

Samir S. Shah, MD, MSCE
Director, Division of Hospital Medicine
James M. Ewell Endowed Chair
Attending Physician in Hospital Medicine & Infectious Diseases
Chief Metrics Officer
Cincinnati Children’s Hospital Medical Center
Professor, Department of Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Bone and Joint Infections

Mark Shen, MD, MBA, FAAP, SFHM
Associate Professor of Pediatrics
Dell Medical School at the University of Texas at Austin
Austin, TX
Leadership in Healthcare

Tamara Simon, MD, MSPH, FAAP
Principal Investigator, Center for Clinical and Translational Research
Seattle Children’s Research Institute
Associate Professor of Pediatrics
Divisions of Hospital Medicine and General Pediatrics, Department of Pediatrics
University of Washington
Seattle, WA
Child with Medical Complexity

Amit Singh, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Division of Pediatric Hospital Medicine, Department of Pediatrics
Stanford University School of Medicine
Stanford, CA
Communication

Karen Smith, MD, MEd, SFHM, FAAP
Chief, Division of Pediatric Hospital Medicine
Children’s National Medical Center
Associate Professor of Pediatrics
The George Washington School of Medicine and Health Sciences
Washington, DC
Business Practices

Nita Srinivas, MD
Pediatric Hospitalist and Infectious Disease Specialist
Fellowship Director, Pediatric Hospital Medicine
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Stanford University School of Medicine
Stanford, CA
Fever of Unknown Origin

Rajendu Srivastava, MD, FRCP(C), MPH
Primary Children’s Medical Center
Assistant Vice President of Research and Medical Director of the Office of Research
Intermountain Healthcare Inc.
Professor of Pediatrics
University of Utah Health Sciences
Salt Lake City, UT
Research

Lynne Sterni, MD
Pediatric Anesthesiology and Pain Medicine
Naval Medical Center San Diego
Assistant Professor
Uniformed Services University School of Health Sciences
San Diego, CA
Pain Management

E. Douglas Thompson Jr, MD, FAAP
Chief, Section of Hospital Medicine
Associate Chair, Access and Partnerships
St. Christopher’s Hospital for Children
Associate Professor of Pediatrics
Drexel University School of Medicine and Health Sciences
Philadelphia, PA
Sickle Cell Disease

Joanna Thomson, MD, MPH, FAAP
Associate Fellowship Program Director, Pediatric Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Assistant Professor, Department of Pediatrics
University of Cincinnati School of Medicine
Cincinnati, OH
Acute Respiratory Failure

Joel Tieder, MD, MPH
Seattle Children’s Hospital
Associate Professor of Pediatrics, Division of Hospital Medicine
University of Washington School of Medicine
Seattle, WA
Brief Resolved Unexplained Event

Adriana Tremoulet, MD, MAS
Associate Director, Kawasaki Disease Research Center
Division of Host-Microbe Systems and Therapeutics
Pediatric Infectious Diseases and Kawasaki Disease
Associate Professor of Pediatrics, University of California San Diego
San Diego, CA
Kawasaki Disease

Marie E. Wang, MD, MPH, FAAP
Associate Fellowship Program Director, Pediatric Hospital Medicine
Lucile Packard Children’s Hospital
Clinical Assistant Professor 
Stanford University School of Medicine
Stanford, CA
Central Nervous System Infections

Ronald Williams, MD, FAAP, FACP
Director, Combined Internal Medicine/Pediatrics Residency Program
Penn State Hershey Children’s Hospital
Professor of Pediatrics and Medicine
Penn State College of Medicine
Hershey, PA
Head and Neck Disorders

Susan Wu, MD, FAAP
Children’s Hospital Los Angeles
Associate Professor of Clinical Pediatrics
Division of Hospital Medicine, Department of Pediatrics
USC Keck School of Medicine
Los Angeles, CA
Bronchiolitis

Sandra Gage, MD, PhD, FAAP, SFHM
Associate Division Chief and Associate Fellowship Director
Division of Hospital Medicine
Phoenix Children’s Hospital
Clinical Associate Professor
University of Arizona College of Medicine – Phoenix
Department of Child Health
Phoenix, AZ

Jennifer Maniscalco, MD, MPH, MAcM, FAAP
Designated Institutional Official
Johns Hopkins All Children’s Hospital
Assistant Professor
Department of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL

Erin Fisher, MD, MHM, FAAP
Medical Director Quality Improvement
Rady Children’s Hospital
Professor of Clinical Pediatrics
Director of Pediatric Quality and Safety Graduate Medical Education
Fellowship Director and Division Director, Pediatric Hospital Medicine
University of California San Diego School of Medicine
Department of Pediatrics
San Diego, CA

Sofia Teferi, MD, FAAP, SFHM
Physician Executive
Richmond, VA

ASSOCIATE EDITORS

Francisco Alvarez, MD, FAAP
Associate Chief, Regional Pediatric Hospital Medicine Programs
Lucile Packard Children’s Hospital
Clinical Associate Professor
Stanford School of Medicine
Stanford, CA 

Michael Burke, MD (1957 – 2019)
In memory: Chairman of Pediatrics
Saint Agnes Hospital
Associate Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD

Weijen Chang, MD
Division Chief, Pediatric Hospital Medicine
Vice Chair for Clinical Affairs, Department of Pediatrics
Baystate Children’s Hospital
Associate Professor of Pediatrics
University of Massachusetts Medical School-Baystate
Springfield, MA

Vineeta Mittal, MD, MBA
Imm. Past President of the Medical/Dental Staff
Children’s Medical Center
Associate Professor of Pediatrics
Director of Pediatric Hospital Medicine
Department of Pediatrics
UT Southwestern Medical Center & Children’s Health System, Dallas
Dallas, TX

Anand Sekaran, MD
Associate Chair of Pediatrics, Clinical Affairs
Division Chief, Hospital Medicine
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Hartford, CT

Amit Singh, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Division of Pediatric Hospital Medicine
Department of Pediatrics
Stanford University School of Medicine
Stanford, CA

Academic Pediatric Association Hospital Medicine Special Interest Group

American Academy of Pediatrics

• Committee on Psychological Aspects of Child and Family Health
• Council on Children with Disabilities
• Council on Community Pediatrics
• Disaster Preparedness Advisory Council
• Family Partnerships Network
• Section on Anesthesiology and Pain Medicine
• Section on Breastfeeding
• Section on Cardiology and Cardiac Surgery
• Section on Critical Care
• Section on Hematology/Oncology
• Section on Hospice and Palliative Medicine
• Section on Hospital Medicine
• Section on LGBT Health and Wellness
• Section on Medicine-Pediatrics
• Section on Nephrology
• Section on Neurology
• Section on Pediatric Trainees
• Section on Surgery
• Section on Transport Medicine
• Section on Urology

Association of Pediatric Program Directors Curriculum Committee

Society of Hospital Medicine Pediatrics Special Interest Group

Society of Hospital Medicine Medicine-Pediatrics Special Interest Group

Francisco Alvarez, MD
Associate Chief, Regional Pediatric Hospitalist Programs
Lucile Packard Children’s Hospital
Clinical Associate Professor
Stanford University School of Medicine
Stanford, CA
Fever of Unknown Origin

Brian Alverson, MD
Director, Division of Pediatric Hospital Medicine
Hasbro Children’s Hospital
Professor of Pediatrics
Alpert School of Medicine, Brown University
Providence, RI
Pneumonia

Eric Balighian, MD
Director, Pediatric Emergency Department
St. Agnes Hospital
Asistant Professor, Department of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD
Acute Abdominal Pain and Acute Abdomen

Julia Beauchamp-Walters, MD
Medical Director, Helen Bernardy Center for Medically Fragile Children
Medical Director, Home Care
Co-Medical Director, Emergency Transport Program
Rady Children’s Hospital
Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Feeding Tubes
Pediatric Interfacility Transport

Eric Biondi, MD, MS
Director, Pediatric Hospital Medicine Division
Johns Hopkins Children’s Center
Associate Professor of Pediatrics
The Johns Hopkins Hospital University School of Medicine
Baltimore, MD
Neonatal Fever

Rebecca Blankenberg, MD, MPH
Associate Chair of Education
Stanford Lucile Packard Children’s Hospital
Clinical Associate Professor of Pediatrics and Emergency Medicine
Stanford University School of Medicine
Stanford, CA
Education

Colin Bridgeman, MD
Penn State Children’s Hospital
Assistant Professor of Pediatrics
Division of General Inpatient Pediatrics
Penn State College of Medicine
Hershey, PA
Head and Neck Disorders

Jeffrey Brown, MD, MPH, CAP, FAAP
Texas Newborn Services/Pediatrix Medical Group
Clinical Professor of Pediatrics
University of Colorado School of Medicine
Fort Worth, TX
Business Practices

April O. Buchanan, MD
Associate Dean for Curriculum
Prisma Health Children’s Hospital at Greenville
Associate Professor of Clinical Pediatrics
University of South Carolina School of Medicine
Greenville, SC
Sepsis and Shock

Douglas Carlson, MD
Medical Director
HSHS St. John’s Children’s Hospital
Professor and Chair of Pediatrics
Southern Illinois University School of Medicine
Springfield, MO
Procedural Sedation

Pearl Chang, MD
Seattle Children’s Hospital
Assistant Professor
Department of Pediatrics, University of Washington
Seattle, WA
Neonatal Jaundice

Eric Coon, MD, MS
Co-Director, Pediatric Hospital Medicine Fellowship
Primary Children’s Medical Center
Assistant Professor of Pediatrics
University of Utah Health Science
Salt Lake City, UT
Research

Yasmeen N. Daud, MD
St. Louis Children’s Hospital
Associate Professor of Pediatrics
Washington University School of Medicine
St. Louise, MO
Oxygen Delivery and Airway Management

Sarah Denniston, MD, FAAP
Fellowship Director, Pediatric Hospital Medicine
The Floating Hospital for Children at Tufts Medical Center
Assistant Professor of Pediatrics
Tufts University School of Medicine
Associate DIO for Quality and Safety
Tufts Medical Center
Boston, MA
Peri-procedural Care

Craig C. DeWolfe, MD, MEd, FAAP
Children’s National Health System
Director of Medical Student Education in Pediatrics
Associate Professor of Pediatrics,
George Washington University School of Medicine
Washington, DC
Brief Resolved Unexplained Event

Stephanie Anne Deutsch, MD, MS, FAAP
Section Chief, Child Abuse Pediatrics
Nemours/Alfred I. duPont Hospital for Children
Co-medical Director, CARE (Children at Risk Evaluation) Program
Assistant Clinical Professor of Pediatrics
Sidney Kimmel Medical College at Thomas Jefferson University
Wilmington, Delaware
Child Abuse and Neglect

Ami Doshi, MD
Medical Director, Inpatient Palliative Care Program
Rady Children’s Hospital San Diego
Clinical Associate Professor of Pediatrics
University of California San Diego School of Medicine
San Diego, CA
Palliative Care and Hospice

Erin Fisher, MD, FAAP, MHM
Medical Director, Quality Improvement
Rady Children’s Hospital San Diego
Professor of Clinical Pediatrics
Director, Pediatric Quality and Safety Graduate Medical Education
Fellowship Director and Division Director, Pediatric Hospital Medicine
University of California San Diego School of Medicine
San Diego, CA
Quality Improvement

Sandra Gage, MD, PhD, FAAP, SFHM
Associate Division Chief and Associate Fellowship Director
Division of Hospital Medicine
Phoenix Children’s Hospital
Clinical Associate Professor
University of Arizona College of Medicine – Phoenix
Department of Child Health
Phoenix, AZ
Acute Gastroenteritis
Gastrointestinal and Digestive Disorders

Mary Pat Gallagher, MD
Director, Pediatric Diabetes Center
Division of Pediatric Endocrinology, Hassenfeld Children’s Hospital
Assistant Professor
Department of Pediatrics
NYU Langone
New York, NY
Diabetes Mellitus

Amrit Gill, MD
Cleveland Clinic Children’s Hospital
Clinical Assistant Professor of Pediatrics
Case Western Reserve University School of Medicine
Cleveland, OH
Patient Safety

Veena Goel Jones, MD, FAAP
Medical Director, Digital Patient Experience, Sutter Health
Sutter Palo Alto Medical Foundation
Palo Alto, CA
Health Information Technology

Jeffrey Grill, MD
Vice Chair, Community Relations and Outreach
Chief, Division of Pediatric Hospital Medicine
Director, Just for Kids Hospitalist Service
Norton Children’s Hospital
Professor, Department of Pediatrics
University of Louisville School of Medicine
Louisville, KY
Constipation

Arun Gupta, MD
Director, Neonatal Hospitalist Program
Lucile Packard Children’s Hospital Stanford
Clinical Associate Professor, Pediatrics
Stanford University School of Medicine
Stanford, CA
Newborn Care and Delivery Room Management

Brian F Herbst Jr, MD
Medical Director, Hospital Medicine Adult Care
Division of Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Assistant Professor of Internal Medicine and Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Adolescent and Young Adult Medicine

Daniel Hershey, MD, SFHM
Rady Children’s Hospital
Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Non-invasive Monitoring

Kim Hoang, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Stanford University School of Medicine
Stanford, CA
Education

Alison Volpe Holmes, MD, MPH
Children’s Hospital at Dartmouth-Hitchcock
Associate Dean for Student Affairs, Career Advising
Vice-Chair for Education, Department of Pediatrics
Associate Professor of Pediatrics and of The Dartmouth Institute
Geisel School of Medicine at Dartmouth
Hanover, NH
Neonatal Abstinence Syndrome/Neonatal Opioid Withdrawal Syndrome

Akshata Hopkins, MD, FAAP, FHM
Director, Pediatric Residency Program
Johns Hopkins All Children’s Hospital
Assistant Professor of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL
High Value Care

Yemisi Jones, MD, FAAP, FHM
Co-Medical Director, Continuing Medical Education
Co-Director Liberty Simulation Education
Cincinnati Children’s Hospital Medical Center
Assistant Professor of Clinical Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Intravenous Access and Phlebotomy

Alisa Khan, MD, MPH
Health Services Researcher
Division of General Pediatrics, Boston Children’s Hospital
Clinical Instructor in Pediatrics
Harvard Medical School
Boston, MA
Family Centered Care

Vivian Lee, MD
Children’s Hospital Los Angeles
Clinical Assistant Professor of Pediatrics
University of Southern California Keck School of Medicine
Los Angeles, CA
Altered Mental Status

Su-Ting T. Li, MD, MPH
Associate Vice Chair of Education
Pediatric Residency Program Director
University of California Davis Children’s Hospital
Professor of Pediatrics
University of California, Davis
Sacramento, CA
Skin and Soft Tissue Infections

Patricia S. Lye, MD, MEd, FAAP
Children’s Hospital of Wisconsin
Professor of Pediatrics, Retired
Medical College of Wisconsin
Milwaukee, WI
Handoffs and Transitions of Care

Tamara Maginot, PhD
Pediatric Psychologist
Program Director, Medical Behavioral Unit
Rady Children’s Hospital San Diego
Assistant Professor, Department of Psychiatry
UC San Diego Eating Disorders Center for Treatment and Research Behavioral Medicine
San Diego, CA
Chronic Behavioral and Psychiatric Conditions

Christopher Maloney, MD, PhD, FAAP
Chief Medical Officer and Senior Vice President
Children’s Hospital & Medical Center
Professor of Pediatrics and Pediatric Critical Care
Department of Pediatrics
University of Nebraska Medical Center College of Medicine
Omaha, NE 
Pediatric Advanced Life Support

Jennifer Maniscalco, MD, MPH, MAcM, FAAP
Designated Institutional Official
Johns Hopkins All Children’s Hospital
Assistant Professor
Department of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL
Failure to Thrive

Elizabeth Mannino Avila, MD
Rady Children’s Hospital
Assistant Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Kawasaki Disease

Alison Markowsky, MD, MSHS, FAAP
Medical Director
Children’s National Pediatric Hospitalist Program at Mary Washington Healthcare
Children’s National Health System
Assistant Professor of Pediatrics
The George Washington University School of Medicine & Health Sciences
Washington, DC
Newborn Care and Delivery Room Management

Michelle Marks, DO, FAAP, SFHM
Chair, Pediatric Hospital Medicine
Cleveland Clinic Children’s Hospital
Clinical Associate Professor
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University
Cleveland, OH
Nutrition

Armand H. Matheny Antommaria, MD, PhD, FAAP
Lee Ault Carter Chair Pediatric Ethics and Pediatric Hospitalist
Cincinnati Children’s Hospital
Associate Professor of Clinical-Affiliated
University of Cincinnati School of Medicine
Cincinnati, OH
Ethics

Erich Maul, MD
Division Chief, Hospital Medicine
Medical Director, Acute Care and Progressive Care
Kentucky Children’s Hospital
Professor of Pediatrics
University of Kentucky School of Medicine
Lexington, KY
Electrocardiogram Interpretation

Rusty McCulloh, MD
Chief, Division of Hospital Medicine
Children’s Hospital & Medical Center
Associate Professor, Division of Hospital Medicine
University of Nebraska College of Medicine
Omaha, NE
Infection Control and Antimicrobial Stewardship

Anjna Melwani, MD
Director, Preoperative Care Clinic
Children’s National Medical Center
Associate Professor of Pediatrics
George Washington University School of Medicine and Health Sciences
Washington, DC
Consultation and Co-management

Christopher Miller, MD
Pediatric Allergist
Children’s Mercy Hospitals and Clinics
Assistant Professor of Pediatrics
Section of Allergy and Immunology
University of Missouri-Kansas City School of Medicine
Kansas City, MO
Asthma

Vineeta Mittal, MD, MBA
Imm. Past President of the Medical/Dental Staff
Children’s Medical Center
Associate Professor of Pediatrics
Director of Pediatric Hospital Medicine
Department of Pediatrics
UT Southwestern Medical Center & Children’s Health System Dallas
Dallas, TX
Acute Respiratory Failure

Beth Natt, MD, MPH, FAAP, SFHM
Director, Pediatric Hospital Medicine, Regional Programs
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Farmington, CT
Bladder Catheterization and Interpretation of Urinalysis

Jennifer O’Toole, MD, MEd, FAAP, SFHM
Program Director, Internal Medicine – Pediatrics Residency
Director of Education, Division of Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Associate Professor of Pediatrics and Internal Medicine
University of Cincinnati College of Medicine
Cincinnati, OH
Adolescent and Young Adult Medicine

Mary Ottolini, MD, MPH, MEd, FAAP
George W. Hallett Chair of Pediatrics
Barbara Bush Children’s Hospital at Maine Medical Center
Professor of Pediatrics
Tufts University School of Medicine
Portland, ME
Fluid and Electrolyte Management

Jack Percelay, MD, MPH, FAAP, MHM
Stanford Lucile Packard Children’s Hospital
Clinical Associate Professor of Pediatrics
Stanford University School of Medicine
Stanford, CA
Advocacy
Seizures

Shannon Phillips, MD, MPH
Chief Patient Safety and Experience Officer
Primary Children’s Medical Center
Intermountain Healthcare, Inc.
Adjunct Associate Professor of Pediatrics
University of Utah Health Sciences
Salt Lake City, UT
Patient Safety

David Pressel, MD, PhD, FAAP, FHM
Medical Director, Pediatric Hospitalist Program
Capital Health Medical Center- Hopewell
Pennington, NJ
Acute Behavioral and Psychiatric Conditions
Child Abuse and Neglect

Ricardo Quinonez, MD, FAAP
Chief, Pediatric Hospital Medicine
Texas Children’s Hospital
Associate Professor of Pediatrics
Baylor College of Medicine
Houston, TX
High Value Care

Shawn Ralston, MA, MD, MS
Johns Hopkins Children’s Center
Editor, Hospital Pediatrics, American Academy of Pediatrics
Associate Professor of Pediatrics
Division of Pediatric Quality and Safety
The Johns Hopkins Hospital University School of Medicine
Baltimore, MD
Evidence Based Medicine

David I. Rappaport, MD, FAAP, FHM
Associate Residency Program Director
Division of General Pediatrics
Nemours/AI duPont Hospital for Children
Wilmington, DE
Associate Professor of Pediatrics
Sidney Kimmel Medical College at Jefferson
Philadelphia, PA
Consultation and Co-management

Daniel Rauch, MD, FAAP, SFHM
Chief, Pediatric Hospital Medicine
The Floating Hospital for Children at Tufts Medical Center.
Professor of Pediatrics
Tufts University School of Medicine
Boston, MA
Preventive Care Services

Kyung (Kay) Rhee, MD, MSc, MA
Director of Research, Division of Pediatric Hospital Medicine
Medical Director, Medical Behavioral Unit
Rady Children’s Hospital San Diego
Professor of Clinical Pediatrics
Department of Pediatrics, Division of General Academic Pediatrics, Developmental Pediatrics, and Center for Community Health
University of San Diego School of Medicine
San Diego, CA
Chronic Behavioral and Psychiatric Conditions

Jeffrey Riese, MD
Associate Pediatric Residency Program Director
Hasbro Children’s Hospital
Associate Professor of Pediatrics
Warren Alpert School of Medicine at Brown University
Providence, RI
Neonatal Fever

Ken Roberts, MD, FAAP
Professor Emeritus of Pediatrics
University of North Carolina School of Medicine
Chapel Hill, NC
Urinary Tract Infections

Amanda Rogers, MD
Associate Pediatric Residency Program Director
Children’s Hospital of Wisconsin
Assistant Professor, Section of Hospital Medicine
Medical College of Wisconsin
Milwaukee, WI
Lumbar Puncture

Rebecca E. Rosenberg, MD, MPH
Chief, Section of Hospital Medicine, Division of General Pediatrics
Hassenfeld Children’s Hospital at NYU Langone Health
Associate Professor of Pediatrics
NYU School of Medicine
New York, NY
Peri-procedural Care

Michael Ruhlen, MD, MHCM, FHM, FACHE
Vice President, Division of Medical Education
Vice Chair, RRC ACGME
Atrium Health System
Charlotte, NC
Legal Issues and Risk Management

Christopher J. Russell, MD, MS, FAAP
Research Director, Division of Hospital Medicine
Children’s Hospital Los Angeles
Assistant Professor of Clinical Pediatrics
Keck School of Medicine, University of Southern California
Los Angeles, CA
Child with Medical Complexity

Christopher Russo, MD
Director of Pediatrics
Central Lynchburg General Hospital
Assistant Professor of Pediatrics
Liberty University College of Osteopathic Medicine
Lynchburg, VA
Advocacy

Klint M. Schwenk, MD, MBA, FAAP, FHM
Associate Division Chief, Pediatric Hospital Medicine
Norton Children’s Hospital
Associate Professor of Pediatrics
University of Louisville
Louisville, KY
Acute Gastroenteritis
Gastrointestinal and Digestive Disorders

Anand Sekaran, MD, FAAP
Associate Chair of Pediatrics, Clinical Affairs
Division Chief, Hospital Medicine
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Hartford, CT
Diagnostic Imaging

Kristin A. Shadman, MD, FAAP
American Family Children’s Hospital
Associate Professor of Pediatrics
Division of Hospital Medicine
University of Wisconsin School of Medicine and Public Health
Madison, WI
Oxygen Delivery and Airway Management

Samir S. Shah, MD, MSCE
Director, Division of Hospital Medicine
James M. Ewell Endowed Chair
Attending Physician in Hospital Medicine & Infectious Diseases
Chief Metrics Officer
Cincinnati Children’s Hospital Medical Center
Professor, Department of Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Bone and Joint Infections

Mark Shen, MD, MBA, FAAP, SFHM
Associate Professor of Pediatrics
Dell Medical School at the University of Texas at Austin
Austin, TX
Leadership in Healthcare

Tamara Simon, MD, MSPH, FAAP
Principal Investigator, Center for Clinical and Translational Research
Seattle Children’s Research Institute
Associate Professor of Pediatrics
Divisions of Hospital Medicine and General Pediatrics, Department of Pediatrics
University of Washington
Seattle, WA
Child with Medical Complexity

Amit Singh, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Division of Pediatric Hospital Medicine, Department of Pediatrics
Stanford University School of Medicine
Stanford, CA
Communication

Karen Smith, MD, MEd, SFHM, FAAP
Chief, Division of Pediatric Hospital Medicine
Children’s National Medical Center
Associate Professor of Pediatrics
The George Washington School of Medicine and Health Sciences
Washington, DC
Business Practices

Nita Srinivas, MD
Pediatric Hospitalist and Infectious Disease Specialist
Fellowship Director, Pediatric Hospital Medicine
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Stanford University School of Medicine
Stanford, CA
Fever of Unknown Origin

Rajendu Srivastava, MD, FRCP(C), MPH
Primary Children’s Medical Center
Assistant Vice President of Research and Medical Director of the Office of Research
Intermountain Healthcare Inc.
Professor of Pediatrics
University of Utah Health Sciences
Salt Lake City, UT
Research

Lynne Sterni, MD
Pediatric Anesthesiology and Pain Medicine
Naval Medical Center San Diego
Assistant Professor
Uniformed Services University School of Health Sciences
San Diego, CA
Pain Management

E. Douglas Thompson Jr, MD, FAAP
Chief, Section of Hospital Medicine
Associate Chair, Access and Partnerships
St. Christopher’s Hospital for Children
Associate Professor of Pediatrics
Drexel University School of Medicine and Health Sciences
Philadelphia, PA
Sickle Cell Disease

Joanna Thomson, MD, MPH, FAAP
Associate Fellowship Program Director, Pediatric Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Assistant Professor, Department of Pediatrics
University of Cincinnati School of Medicine
Cincinnati, OH
Acute Respiratory Failure

Joel Tieder, MD, MPH
Seattle Children’s Hospital
Associate Professor of Pediatrics, Division of Hospital Medicine
University of Washington School of Medicine
Seattle, WA
Brief Resolved Unexplained Event

Adriana Tremoulet, MD, MAS
Associate Director, Kawasaki Disease Research Center
Division of Host-Microbe Systems and Therapeutics
Pediatric Infectious Diseases and Kawasaki Disease
Associate Professor of Pediatrics, University of California San Diego
San Diego, CA
Kawasaki Disease

Marie E. Wang, MD, MPH, FAAP
Associate Fellowship Program Director, Pediatric Hospital Medicine
Lucile Packard Children’s Hospital
Clinical Assistant Professor 
Stanford University School of Medicine
Stanford, CA
Central Nervous System Infections

Ronald Williams, MD, FAAP, FACP
Director, Combined Internal Medicine/Pediatrics Residency Program
Penn State Hershey Children’s Hospital
Professor of Pediatrics and Medicine
Penn State College of Medicine
Hershey, PA
Head and Neck Disorders

Susan Wu, MD, FAAP
Children’s Hospital Los Angeles
Associate Professor of Clinical Pediatrics
Division of Hospital Medicine, Department of Pediatrics
USC Keck School of Medicine
Los Angeles, CA
Bronchiolitis

Sandra Gage, MD, PhD, FAAP, SFHM
Associate Division Chief and Associate Fellowship Director
Division of Hospital Medicine
Phoenix Children’s Hospital
Clinical Associate Professor
University of Arizona College of Medicine – Phoenix
Department of Child Health
Phoenix, AZ

Jennifer Maniscalco, MD, MPH, MAcM, FAAP
Designated Institutional Official
Johns Hopkins All Children’s Hospital
Assistant Professor
Department of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL

Erin Fisher, MD, MHM, FAAP
Medical Director Quality Improvement
Rady Children’s Hospital
Professor of Clinical Pediatrics
Director of Pediatric Quality and Safety Graduate Medical Education
Fellowship Director and Division Director, Pediatric Hospital Medicine
University of California San Diego School of Medicine
Department of Pediatrics
San Diego, CA

Sofia Teferi, MD, FAAP, SFHM
Physician Executive
Richmond, VA

ASSOCIATE EDITORS

Francisco Alvarez, MD, FAAP
Associate Chief, Regional Pediatric Hospital Medicine Programs
Lucile Packard Children’s Hospital
Clinical Associate Professor
Stanford School of Medicine
Stanford, CA 

Michael Burke, MD (1957 – 2019)
In memory: Chairman of Pediatrics
Saint Agnes Hospital
Associate Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD

Weijen Chang, MD
Division Chief, Pediatric Hospital Medicine
Vice Chair for Clinical Affairs, Department of Pediatrics
Baystate Children’s Hospital
Associate Professor of Pediatrics
University of Massachusetts Medical School-Baystate
Springfield, MA

Vineeta Mittal, MD, MBA
Imm. Past President of the Medical/Dental Staff
Children’s Medical Center
Associate Professor of Pediatrics
Director of Pediatric Hospital Medicine
Department of Pediatrics
UT Southwestern Medical Center & Children’s Health System, Dallas
Dallas, TX

Anand Sekaran, MD
Associate Chair of Pediatrics, Clinical Affairs
Division Chief, Hospital Medicine
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Hartford, CT

Amit Singh, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Division of Pediatric Hospital Medicine
Department of Pediatrics
Stanford University School of Medicine
Stanford, CA

Academic Pediatric Association Hospital Medicine Special Interest Group

American Academy of Pediatrics

• Committee on Psychological Aspects of Child and Family Health
• Council on Children with Disabilities
• Council on Community Pediatrics
• Disaster Preparedness Advisory Council
• Family Partnerships Network
• Section on Anesthesiology and Pain Medicine
• Section on Breastfeeding
• Section on Cardiology and Cardiac Surgery
• Section on Critical Care
• Section on Hematology/Oncology
• Section on Hospice and Palliative Medicine
• Section on Hospital Medicine
• Section on LGBT Health and Wellness
• Section on Medicine-Pediatrics
• Section on Nephrology
• Section on Neurology
• Section on Pediatric Trainees
• Section on Surgery
• Section on Transport Medicine
• Section on Urology

Association of Pediatric Program Directors Curriculum Committee

Society of Hospital Medicine Pediatrics Special Interest Group

Society of Hospital Medicine Medicine-Pediatrics Special Interest Group

Francisco Alvarez, MD
Associate Chief, Regional Pediatric Hospitalist Programs
Lucile Packard Children’s Hospital
Clinical Associate Professor
Stanford University School of Medicine
Stanford, CA
Fever of Unknown Origin

Brian Alverson, MD
Director, Division of Pediatric Hospital Medicine
Hasbro Children’s Hospital
Professor of Pediatrics
Alpert School of Medicine, Brown University
Providence, RI
Pneumonia

Eric Balighian, MD
Director, Pediatric Emergency Department
St. Agnes Hospital
Asistant Professor, Department of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD
Acute Abdominal Pain and Acute Abdomen

Julia Beauchamp-Walters, MD
Medical Director, Helen Bernardy Center for Medically Fragile Children
Medical Director, Home Care
Co-Medical Director, Emergency Transport Program
Rady Children’s Hospital
Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Feeding Tubes
Pediatric Interfacility Transport

Eric Biondi, MD, MS
Director, Pediatric Hospital Medicine Division
Johns Hopkins Children’s Center
Associate Professor of Pediatrics
The Johns Hopkins Hospital University School of Medicine
Baltimore, MD
Neonatal Fever

Rebecca Blankenberg, MD, MPH
Associate Chair of Education
Stanford Lucile Packard Children’s Hospital
Clinical Associate Professor of Pediatrics and Emergency Medicine
Stanford University School of Medicine
Stanford, CA
Education

Colin Bridgeman, MD
Penn State Children’s Hospital
Assistant Professor of Pediatrics
Division of General Inpatient Pediatrics
Penn State College of Medicine
Hershey, PA
Head and Neck Disorders

Jeffrey Brown, MD, MPH, CAP, FAAP
Texas Newborn Services/Pediatrix Medical Group
Clinical Professor of Pediatrics
University of Colorado School of Medicine
Fort Worth, TX
Business Practices

April O. Buchanan, MD
Associate Dean for Curriculum
Prisma Health Children’s Hospital at Greenville
Associate Professor of Clinical Pediatrics
University of South Carolina School of Medicine
Greenville, SC
Sepsis and Shock

Douglas Carlson, MD
Medical Director
HSHS St. John’s Children’s Hospital
Professor and Chair of Pediatrics
Southern Illinois University School of Medicine
Springfield, MO
Procedural Sedation

Pearl Chang, MD
Seattle Children’s Hospital
Assistant Professor
Department of Pediatrics, University of Washington
Seattle, WA
Neonatal Jaundice

Eric Coon, MD, MS
Co-Director, Pediatric Hospital Medicine Fellowship
Primary Children’s Medical Center
Assistant Professor of Pediatrics
University of Utah Health Science
Salt Lake City, UT
Research

Yasmeen N. Daud, MD
St. Louis Children’s Hospital
Associate Professor of Pediatrics
Washington University School of Medicine
St. Louise, MO
Oxygen Delivery and Airway Management

Sarah Denniston, MD, FAAP
Fellowship Director, Pediatric Hospital Medicine
The Floating Hospital for Children at Tufts Medical Center
Assistant Professor of Pediatrics
Tufts University School of Medicine
Associate DIO for Quality and Safety
Tufts Medical Center
Boston, MA
Peri-procedural Care

Craig C. DeWolfe, MD, MEd, FAAP
Children’s National Health System
Director of Medical Student Education in Pediatrics
Associate Professor of Pediatrics,
George Washington University School of Medicine
Washington, DC
Brief Resolved Unexplained Event

Stephanie Anne Deutsch, MD, MS, FAAP
Section Chief, Child Abuse Pediatrics
Nemours/Alfred I. duPont Hospital for Children
Co-medical Director, CARE (Children at Risk Evaluation) Program
Assistant Clinical Professor of Pediatrics
Sidney Kimmel Medical College at Thomas Jefferson University
Wilmington, Delaware
Child Abuse and Neglect

Ami Doshi, MD
Medical Director, Inpatient Palliative Care Program
Rady Children’s Hospital San Diego
Clinical Associate Professor of Pediatrics
University of California San Diego School of Medicine
San Diego, CA
Palliative Care and Hospice

Erin Fisher, MD, FAAP, MHM
Medical Director, Quality Improvement
Rady Children’s Hospital San Diego
Professor of Clinical Pediatrics
Director, Pediatric Quality and Safety Graduate Medical Education
Fellowship Director and Division Director, Pediatric Hospital Medicine
University of California San Diego School of Medicine
San Diego, CA
Quality Improvement

Sandra Gage, MD, PhD, FAAP, SFHM
Associate Division Chief and Associate Fellowship Director
Division of Hospital Medicine
Phoenix Children’s Hospital
Clinical Associate Professor
University of Arizona College of Medicine – Phoenix
Department of Child Health
Phoenix, AZ
Acute Gastroenteritis
Gastrointestinal and Digestive Disorders

Mary Pat Gallagher, MD
Director, Pediatric Diabetes Center
Division of Pediatric Endocrinology, Hassenfeld Children’s Hospital
Assistant Professor
Department of Pediatrics
NYU Langone
New York, NY
Diabetes Mellitus

Amrit Gill, MD
Cleveland Clinic Children’s Hospital
Clinical Assistant Professor of Pediatrics
Case Western Reserve University School of Medicine
Cleveland, OH
Patient Safety

Veena Goel Jones, MD, FAAP
Medical Director, Digital Patient Experience, Sutter Health
Sutter Palo Alto Medical Foundation
Palo Alto, CA
Health Information Technology

Jeffrey Grill, MD
Vice Chair, Community Relations and Outreach
Chief, Division of Pediatric Hospital Medicine
Director, Just for Kids Hospitalist Service
Norton Children’s Hospital
Professor, Department of Pediatrics
University of Louisville School of Medicine
Louisville, KY
Constipation

Arun Gupta, MD
Director, Neonatal Hospitalist Program
Lucile Packard Children’s Hospital Stanford
Clinical Associate Professor, Pediatrics
Stanford University School of Medicine
Stanford, CA
Newborn Care and Delivery Room Management

Brian F Herbst Jr, MD
Medical Director, Hospital Medicine Adult Care
Division of Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Assistant Professor of Internal Medicine and Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Adolescent and Young Adult Medicine

Daniel Hershey, MD, SFHM
Rady Children’s Hospital
Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Non-invasive Monitoring

Kim Hoang, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Stanford University School of Medicine
Stanford, CA
Education

Alison Volpe Holmes, MD, MPH
Children’s Hospital at Dartmouth-Hitchcock
Associate Dean for Student Affairs, Career Advising
Vice-Chair for Education, Department of Pediatrics
Associate Professor of Pediatrics and of The Dartmouth Institute
Geisel School of Medicine at Dartmouth
Hanover, NH
Neonatal Abstinence Syndrome/Neonatal Opioid Withdrawal Syndrome

Akshata Hopkins, MD, FAAP, FHM
Director, Pediatric Residency Program
Johns Hopkins All Children’s Hospital
Assistant Professor of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL
High Value Care

Yemisi Jones, MD, FAAP, FHM
Co-Medical Director, Continuing Medical Education
Co-Director Liberty Simulation Education
Cincinnati Children’s Hospital Medical Center
Assistant Professor of Clinical Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Intravenous Access and Phlebotomy

Alisa Khan, MD, MPH
Health Services Researcher
Division of General Pediatrics, Boston Children’s Hospital
Clinical Instructor in Pediatrics
Harvard Medical School
Boston, MA
Family Centered Care

Vivian Lee, MD
Children’s Hospital Los Angeles
Clinical Assistant Professor of Pediatrics
University of Southern California Keck School of Medicine
Los Angeles, CA
Altered Mental Status

Su-Ting T. Li, MD, MPH
Associate Vice Chair of Education
Pediatric Residency Program Director
University of California Davis Children’s Hospital
Professor of Pediatrics
University of California, Davis
Sacramento, CA
Skin and Soft Tissue Infections

Patricia S. Lye, MD, MEd, FAAP
Children’s Hospital of Wisconsin
Professor of Pediatrics, Retired
Medical College of Wisconsin
Milwaukee, WI
Handoffs and Transitions of Care

Tamara Maginot, PhD
Pediatric Psychologist
Program Director, Medical Behavioral Unit
Rady Children’s Hospital San Diego
Assistant Professor, Department of Psychiatry
UC San Diego Eating Disorders Center for Treatment and Research Behavioral Medicine
San Diego, CA
Chronic Behavioral and Psychiatric Conditions

Christopher Maloney, MD, PhD, FAAP
Chief Medical Officer and Senior Vice President
Children’s Hospital & Medical Center
Professor of Pediatrics and Pediatric Critical Care
Department of Pediatrics
University of Nebraska Medical Center College of Medicine
Omaha, NE 
Pediatric Advanced Life Support

Jennifer Maniscalco, MD, MPH, MAcM, FAAP
Designated Institutional Official
Johns Hopkins All Children’s Hospital
Assistant Professor
Department of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL
Failure to Thrive

Elizabeth Mannino Avila, MD
Rady Children’s Hospital
Assistant Clinical Professor of Pediatrics
University of California, San Diego
San Diego, CA
Kawasaki Disease

Alison Markowsky, MD, MSHS, FAAP
Medical Director
Children’s National Pediatric Hospitalist Program at Mary Washington Healthcare
Children’s National Health System
Assistant Professor of Pediatrics
The George Washington University School of Medicine & Health Sciences
Washington, DC
Newborn Care and Delivery Room Management

Michelle Marks, DO, FAAP, SFHM
Chair, Pediatric Hospital Medicine
Cleveland Clinic Children’s Hospital
Clinical Associate Professor
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University
Cleveland, OH
Nutrition

Armand H. Matheny Antommaria, MD, PhD, FAAP
Lee Ault Carter Chair Pediatric Ethics and Pediatric Hospitalist
Cincinnati Children’s Hospital
Associate Professor of Clinical-Affiliated
University of Cincinnati School of Medicine
Cincinnati, OH
Ethics

Erich Maul, MD
Division Chief, Hospital Medicine
Medical Director, Acute Care and Progressive Care
Kentucky Children’s Hospital
Professor of Pediatrics
University of Kentucky School of Medicine
Lexington, KY
Electrocardiogram Interpretation

Rusty McCulloh, MD
Chief, Division of Hospital Medicine
Children’s Hospital & Medical Center
Associate Professor, Division of Hospital Medicine
University of Nebraska College of Medicine
Omaha, NE
Infection Control and Antimicrobial Stewardship

Anjna Melwani, MD
Director, Preoperative Care Clinic
Children’s National Medical Center
Associate Professor of Pediatrics
George Washington University School of Medicine and Health Sciences
Washington, DC
Consultation and Co-management

Christopher Miller, MD
Pediatric Allergist
Children’s Mercy Hospitals and Clinics
Assistant Professor of Pediatrics
Section of Allergy and Immunology
University of Missouri-Kansas City School of Medicine
Kansas City, MO
Asthma

Vineeta Mittal, MD, MBA
Imm. Past President of the Medical/Dental Staff
Children’s Medical Center
Associate Professor of Pediatrics
Director of Pediatric Hospital Medicine
Department of Pediatrics
UT Southwestern Medical Center & Children’s Health System Dallas
Dallas, TX
Acute Respiratory Failure

Beth Natt, MD, MPH, FAAP, SFHM
Director, Pediatric Hospital Medicine, Regional Programs
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Farmington, CT
Bladder Catheterization and Interpretation of Urinalysis

Jennifer O’Toole, MD, MEd, FAAP, SFHM
Program Director, Internal Medicine – Pediatrics Residency
Director of Education, Division of Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Associate Professor of Pediatrics and Internal Medicine
University of Cincinnati College of Medicine
Cincinnati, OH
Adolescent and Young Adult Medicine

Mary Ottolini, MD, MPH, MEd, FAAP
George W. Hallett Chair of Pediatrics
Barbara Bush Children’s Hospital at Maine Medical Center
Professor of Pediatrics
Tufts University School of Medicine
Portland, ME
Fluid and Electrolyte Management

Jack Percelay, MD, MPH, FAAP, MHM
Stanford Lucile Packard Children’s Hospital
Clinical Associate Professor of Pediatrics
Stanford University School of Medicine
Stanford, CA
Advocacy
Seizures

Shannon Phillips, MD, MPH
Chief Patient Safety and Experience Officer
Primary Children’s Medical Center
Intermountain Healthcare, Inc.
Adjunct Associate Professor of Pediatrics
University of Utah Health Sciences
Salt Lake City, UT
Patient Safety

David Pressel, MD, PhD, FAAP, FHM
Medical Director, Pediatric Hospitalist Program
Capital Health Medical Center- Hopewell
Pennington, NJ
Acute Behavioral and Psychiatric Conditions
Child Abuse and Neglect

Ricardo Quinonez, MD, FAAP
Chief, Pediatric Hospital Medicine
Texas Children’s Hospital
Associate Professor of Pediatrics
Baylor College of Medicine
Houston, TX
High Value Care

Shawn Ralston, MA, MD, MS
Johns Hopkins Children’s Center
Editor, Hospital Pediatrics, American Academy of Pediatrics
Associate Professor of Pediatrics
Division of Pediatric Quality and Safety
The Johns Hopkins Hospital University School of Medicine
Baltimore, MD
Evidence Based Medicine

David I. Rappaport, MD, FAAP, FHM
Associate Residency Program Director
Division of General Pediatrics
Nemours/AI duPont Hospital for Children
Wilmington, DE
Associate Professor of Pediatrics
Sidney Kimmel Medical College at Jefferson
Philadelphia, PA
Consultation and Co-management

Daniel Rauch, MD, FAAP, SFHM
Chief, Pediatric Hospital Medicine
The Floating Hospital for Children at Tufts Medical Center.
Professor of Pediatrics
Tufts University School of Medicine
Boston, MA
Preventive Care Services

Kyung (Kay) Rhee, MD, MSc, MA
Director of Research, Division of Pediatric Hospital Medicine
Medical Director, Medical Behavioral Unit
Rady Children’s Hospital San Diego
Professor of Clinical Pediatrics
Department of Pediatrics, Division of General Academic Pediatrics, Developmental Pediatrics, and Center for Community Health
University of San Diego School of Medicine
San Diego, CA
Chronic Behavioral and Psychiatric Conditions

Jeffrey Riese, MD
Associate Pediatric Residency Program Director
Hasbro Children’s Hospital
Associate Professor of Pediatrics
Warren Alpert School of Medicine at Brown University
Providence, RI
Neonatal Fever

Ken Roberts, MD, FAAP
Professor Emeritus of Pediatrics
University of North Carolina School of Medicine
Chapel Hill, NC
Urinary Tract Infections

Amanda Rogers, MD
Associate Pediatric Residency Program Director
Children’s Hospital of Wisconsin
Assistant Professor, Section of Hospital Medicine
Medical College of Wisconsin
Milwaukee, WI
Lumbar Puncture

Rebecca E. Rosenberg, MD, MPH
Chief, Section of Hospital Medicine, Division of General Pediatrics
Hassenfeld Children’s Hospital at NYU Langone Health
Associate Professor of Pediatrics
NYU School of Medicine
New York, NY
Peri-procedural Care

Michael Ruhlen, MD, MHCM, FHM, FACHE
Vice President, Division of Medical Education
Vice Chair, RRC ACGME
Atrium Health System
Charlotte, NC
Legal Issues and Risk Management

Christopher J. Russell, MD, MS, FAAP
Research Director, Division of Hospital Medicine
Children’s Hospital Los Angeles
Assistant Professor of Clinical Pediatrics
Keck School of Medicine, University of Southern California
Los Angeles, CA
Child with Medical Complexity

Christopher Russo, MD
Director of Pediatrics
Central Lynchburg General Hospital
Assistant Professor of Pediatrics
Liberty University College of Osteopathic Medicine
Lynchburg, VA
Advocacy

Klint M. Schwenk, MD, MBA, FAAP, FHM
Associate Division Chief, Pediatric Hospital Medicine
Norton Children’s Hospital
Associate Professor of Pediatrics
University of Louisville
Louisville, KY
Acute Gastroenteritis
Gastrointestinal and Digestive Disorders

Anand Sekaran, MD, FAAP
Associate Chair of Pediatrics, Clinical Affairs
Division Chief, Hospital Medicine
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Hartford, CT
Diagnostic Imaging

Kristin A. Shadman, MD, FAAP
American Family Children’s Hospital
Associate Professor of Pediatrics
Division of Hospital Medicine
University of Wisconsin School of Medicine and Public Health
Madison, WI
Oxygen Delivery and Airway Management

Samir S. Shah, MD, MSCE
Director, Division of Hospital Medicine
James M. Ewell Endowed Chair
Attending Physician in Hospital Medicine & Infectious Diseases
Chief Metrics Officer
Cincinnati Children’s Hospital Medical Center
Professor, Department of Pediatrics
University of Cincinnati College of Medicine
Cincinnati, OH
Bone and Joint Infections

Mark Shen, MD, MBA, FAAP, SFHM
Associate Professor of Pediatrics
Dell Medical School at the University of Texas at Austin
Austin, TX
Leadership in Healthcare

Tamara Simon, MD, MSPH, FAAP
Principal Investigator, Center for Clinical and Translational Research
Seattle Children’s Research Institute
Associate Professor of Pediatrics
Divisions of Hospital Medicine and General Pediatrics, Department of Pediatrics
University of Washington
Seattle, WA
Child with Medical Complexity

Amit Singh, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Division of Pediatric Hospital Medicine, Department of Pediatrics
Stanford University School of Medicine
Stanford, CA
Communication

Karen Smith, MD, MEd, SFHM, FAAP
Chief, Division of Pediatric Hospital Medicine
Children’s National Medical Center
Associate Professor of Pediatrics
The George Washington School of Medicine and Health Sciences
Washington, DC
Business Practices

Nita Srinivas, MD
Pediatric Hospitalist and Infectious Disease Specialist
Fellowship Director, Pediatric Hospital Medicine
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Stanford University School of Medicine
Stanford, CA
Fever of Unknown Origin

Rajendu Srivastava, MD, FRCP(C), MPH
Primary Children’s Medical Center
Assistant Vice President of Research and Medical Director of the Office of Research
Intermountain Healthcare Inc.
Professor of Pediatrics
University of Utah Health Sciences
Salt Lake City, UT
Research

Lynne Sterni, MD
Pediatric Anesthesiology and Pain Medicine
Naval Medical Center San Diego
Assistant Professor
Uniformed Services University School of Health Sciences
San Diego, CA
Pain Management

E. Douglas Thompson Jr, MD, FAAP
Chief, Section of Hospital Medicine
Associate Chair, Access and Partnerships
St. Christopher’s Hospital for Children
Associate Professor of Pediatrics
Drexel University School of Medicine and Health Sciences
Philadelphia, PA
Sickle Cell Disease

Joanna Thomson, MD, MPH, FAAP
Associate Fellowship Program Director, Pediatric Hospital Medicine
Cincinnati Children’s Hospital Medical Center
Assistant Professor, Department of Pediatrics
University of Cincinnati School of Medicine
Cincinnati, OH
Acute Respiratory Failure

Joel Tieder, MD, MPH
Seattle Children’s Hospital
Associate Professor of Pediatrics, Division of Hospital Medicine
University of Washington School of Medicine
Seattle, WA
Brief Resolved Unexplained Event

Adriana Tremoulet, MD, MAS
Associate Director, Kawasaki Disease Research Center
Division of Host-Microbe Systems and Therapeutics
Pediatric Infectious Diseases and Kawasaki Disease
Associate Professor of Pediatrics, University of California San Diego
San Diego, CA
Kawasaki Disease

Marie E. Wang, MD, MPH, FAAP
Associate Fellowship Program Director, Pediatric Hospital Medicine
Lucile Packard Children’s Hospital
Clinical Assistant Professor 
Stanford University School of Medicine
Stanford, CA
Central Nervous System Infections

Ronald Williams, MD, FAAP, FACP
Director, Combined Internal Medicine/Pediatrics Residency Program
Penn State Hershey Children’s Hospital
Professor of Pediatrics and Medicine
Penn State College of Medicine
Hershey, PA
Head and Neck Disorders

Susan Wu, MD, FAAP
Children’s Hospital Los Angeles
Associate Professor of Clinical Pediatrics
Division of Hospital Medicine, Department of Pediatrics
USC Keck School of Medicine
Los Angeles, CA
Bronchiolitis

Sandra Gage, MD, PhD, FAAP, SFHM
Associate Division Chief and Associate Fellowship Director
Division of Hospital Medicine
Phoenix Children’s Hospital
Clinical Associate Professor
University of Arizona College of Medicine – Phoenix
Department of Child Health
Phoenix, AZ

Jennifer Maniscalco, MD, MPH, MAcM, FAAP
Designated Institutional Official
Johns Hopkins All Children’s Hospital
Assistant Professor
Department of Pediatrics
Johns Hopkins University School of Medicine
St. Petersburg, FL

Erin Fisher, MD, MHM, FAAP
Medical Director Quality Improvement
Rady Children’s Hospital
Professor of Clinical Pediatrics
Director of Pediatric Quality and Safety Graduate Medical Education
Fellowship Director and Division Director, Pediatric Hospital Medicine
University of California San Diego School of Medicine
Department of Pediatrics
San Diego, CA

Sofia Teferi, MD, FAAP, SFHM
Physician Executive
Richmond, VA

ASSOCIATE EDITORS

Francisco Alvarez, MD, FAAP
Associate Chief, Regional Pediatric Hospital Medicine Programs
Lucile Packard Children’s Hospital
Clinical Associate Professor
Stanford School of Medicine
Stanford, CA 

Michael Burke, MD (1957 – 2019)
In memory: Chairman of Pediatrics
Saint Agnes Hospital
Associate Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD

Weijen Chang, MD
Division Chief, Pediatric Hospital Medicine
Vice Chair for Clinical Affairs, Department of Pediatrics
Baystate Children’s Hospital
Associate Professor of Pediatrics
University of Massachusetts Medical School-Baystate
Springfield, MA

Vineeta Mittal, MD, MBA
Imm. Past President of the Medical/Dental Staff
Children’s Medical Center
Associate Professor of Pediatrics
Director of Pediatric Hospital Medicine
Department of Pediatrics
UT Southwestern Medical Center & Children’s Health System, Dallas
Dallas, TX

Anand Sekaran, MD
Associate Chair of Pediatrics, Clinical Affairs
Division Chief, Hospital Medicine
Connecticut Children’s Medical Center
Associate Professor of Pediatrics
University of Connecticut School of Medicine
Hartford, CT

Amit Singh, MD, FAAP
Lucile Packard Children’s Hospital
Clinical Assistant Professor
Division of Pediatric Hospital Medicine
Department of Pediatrics
Stanford University School of Medicine
Stanford, CA

Academic Pediatric Association Hospital Medicine Special Interest Group

American Academy of Pediatrics

• Committee on Psychological Aspects of Child and Family Health
• Council on Children with Disabilities
• Council on Community Pediatrics
• Disaster Preparedness Advisory Council
• Family Partnerships Network
• Section on Anesthesiology and Pain Medicine
• Section on Breastfeeding
• Section on Cardiology and Cardiac Surgery
• Section on Critical Care
• Section on Hematology/Oncology
• Section on Hospice and Palliative Medicine
• Section on Hospital Medicine
• Section on LGBT Health and Wellness
• Section on Medicine-Pediatrics
• Section on Nephrology
• Section on Neurology
• Section on Pediatric Trainees
• Section on Surgery
• Section on Transport Medicine
• Section on Urology

Association of Pediatric Program Directors Curriculum Committee

Society of Hospital Medicine Pediatrics Special Interest Group

Society of Hospital Medicine Medicine-Pediatrics Special Interest Group

Treatment options for atopic dermatitis have evolved significantly in the past several years, but the current guidelines have yet to catch up.

Drs Steven Feldman and Lindsay Strowd, from Wake Forest School of Medicine, discuss gaps in the American Academy of Dermatology treatment guidelines for atopic dermatitis.

The current guidelines have not been updated to include medications approved for atopic dermatitis, including crisaborole, a steroid-sparing ointment used to treat mild to moderate disease in patients 3 months of age and older.

Another drug that has been approved since the 2014 guidelines is the biologic dupilumab, which is a monoclonal antibody that acts on the IL-4 receptor. The agent inhibits the binding of IL-4 receptors to the principal cytokines responsible for mediating the disease. Dupilumab is administered by injection and is approved for patients 6 years and older with moderate to severe disease.

The doctors also discuss therapies for atopic dermatitis currently in development, including topical and oral JAK inhibitors. They agree that the long-term benefit of topical JAK inhibitors may be limited, but that oral JAK inhibitors have the potential to be more effective than dupilumab and more acceptable to patients who do not like injections.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Lindsay C. Strowd, MD, Associate Professor, Vice Chair, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Lindsay C. Strowd, MD, has disclosed no relevant financial relationships.

Treatment options for atopic dermatitis have evolved significantly in the past several years, but the current guidelines have yet to catch up.

Drs Steven Feldman and Lindsay Strowd, from Wake Forest School of Medicine, discuss gaps in the American Academy of Dermatology treatment guidelines for atopic dermatitis.

The current guidelines have not been updated to include medications approved for atopic dermatitis, including crisaborole, a steroid-sparing ointment used to treat mild to moderate disease in patients 3 months of age and older.

Another drug that has been approved since the 2014 guidelines is the biologic dupilumab, which is a monoclonal antibody that acts on the IL-4 receptor. The agent inhibits the binding of IL-4 receptors to the principal cytokines responsible for mediating the disease. Dupilumab is administered by injection and is approved for patients 6 years and older with moderate to severe disease.

The doctors also discuss therapies for atopic dermatitis currently in development, including topical and oral JAK inhibitors. They agree that the long-term benefit of topical JAK inhibitors may be limited, but that oral JAK inhibitors have the potential to be more effective than dupilumab and more acceptable to patients who do not like injections.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Lindsay C. Strowd, MD, Associate Professor, Vice Chair, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Lindsay C. Strowd, MD, has disclosed no relevant financial relationships.

Treatment options for atopic dermatitis have evolved significantly in the past several years, but the current guidelines have yet to catch up.

Drs Steven Feldman and Lindsay Strowd, from Wake Forest School of Medicine, discuss gaps in the American Academy of Dermatology treatment guidelines for atopic dermatitis.

The current guidelines have not been updated to include medications approved for atopic dermatitis, including crisaborole, a steroid-sparing ointment used to treat mild to moderate disease in patients 3 months of age and older.

Another drug that has been approved since the 2014 guidelines is the biologic dupilumab, which is a monoclonal antibody that acts on the IL-4 receptor. The agent inhibits the binding of IL-4 receptors to the principal cytokines responsible for mediating the disease. Dupilumab is administered by injection and is approved for patients 6 years and older with moderate to severe disease.

The doctors also discuss therapies for atopic dermatitis currently in development, including topical and oral JAK inhibitors. They agree that the long-term benefit of topical JAK inhibitors may be limited, but that oral JAK inhibitors have the potential to be more effective than dupilumab and more acceptable to patients who do not like injections.

--

Steven R. Feldman, MD, PhD, Professor, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Steven R. Feldman, MD, PhD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: AbbVie; Alvotech; Advance Medical; Almirall; Arena; Bristol-Myers Squibb; Caremark; Amgen; Celgene; Galderma Laboratories; Gerson Lehrman Group; Guidepoint Global; Helsinn; Janssen; Kikaku; Leo Pharma; Eli Lilly and Company; Merck; Mylan; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sienna; Sun Pharma; Suncare Research; Xenoport
Serve(d) as a speaker for: AbbVie; Amgen; Celgene; Janssen; Leo Pharma; Eli Lilly and Company; Novartis; Ortho Dermatology; Pfizer; Regeneron; Sanofi; Sun Pharma
Receive(d) grant support from: AbbVie; Amgen; Celgene; Galderma Laboratories; Janssen; Eli Lilly and Company; Novartis; Pfizer; Regeneron; Sanofi
Receive(d) royalties from: Informa; UpToDate; Xlibris
Holds stock in: Causa Technologies; Medical Quality Enhancement Corporation
Serves as founder and chief technology officer for: Causa Technologies

Lindsay C. Strowd, MD, Associate Professor, Vice Chair, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina

Lindsay C. Strowd, MD, has disclosed no relevant financial relationships.

The combination of pyrotinib and capecitabine significantly prolonged progression-free survival (PFS), when compared with lapatinib and capecitabine, among patients with previously treated HER2-positive metastatic breast cancer in a phase 3 trial.

PFS was extended by nearly 6 months among patients who received pyrotinib, a novel pan-HER2 inhibitor, combined with capecitabine. Grade 3 diarrhea occurred in nearly 31% of patients receiving the pyrotinib-capecitabine combination, though none of the patients discontinued treatment due to this adverse event.

Binghe Xu, MD, PhD, of the National Cancer Center/Cancer Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, presented these results, from the phase 3 PHOEBE trial, as part of the American Society of Clinical Oncology virtual scientific program.
 

The value of pyrotinib

Although there are already many targeted therapies for HER2-positive metastatic breast cancer, accessibility can be an issue, with drugs such as pertuzumab and trastuzumab emtansine (T-DM1) not available in all regions of the world, according to Dr. Xu.

“Before we initiated this clinical trial, lapatinib plus capecitabine was the only second-line standard of care against HER2-positive metastatic breast cancer in China,” he said.

Based, in part, on results of the PHOEBE trial, the combination of pyrotinib and capecitabine was approved in China as a second-line standard of care for patients with HER2-positive metastatic breast cancer, according to Dr. Xu.

Pyrotinib has now demonstrated “clinical value” in two phase 3 clinical trials, but its value in relation to pertuzumab, T-DM1, tucatinib, trastuzumab deruxtecan, or neratinib is less clear, said Aleix Prat, MD, PhD, of Hospital Clinic of Barcelona.

“Also, in my opinion, the toxicity profile needs attention,” Dr. Prat said in a discussion of the PHOEBE results that was also part of the virtual ASCO meeting.

The 31% incidence of grade 3 diarrhea was “very similar,” he said, to what was seen in PHENIX, another phase 3 trial of pyrotinib plus capecitabine that was presented at the 2019 ASCO annual meeting (J Clin Oncol 37, 2019 suppl; abstr 1001).

“What is the current therapy landscape? In my opinion, today, the first line remains taxane, trastuzumab, and pertuzumab; the second line T-DM1; and the third line tucatinib, trastuzumab, and capecitabine, with other treatment strategies reserved for later lines,” Dr. Prat said.

Study details

PHOEBE included 267 patients with HER2-positive metastatic breast cancer. They had previously received trastuzumab and taxanes, and/or anthracyclines, with up to two prior lines of chemotherapy for metastatic disease.

The patients’ median age was 50 years, 79% had visceral metastases at screening, and about 26% had trastuzumab resistance, Dr. Xu said. Resistance was defined as relapse within 6 months after adjuvant treatment or progression within 3 months of treatment for metastatic disease.

A statistically significant and clinically meaningful improvement was seen in PFS, the primary endpoint of the study, Dr. Xu said.

Median PFS by blinded independent central review was 12.5 months for the pyrotinib-capecitabine combination, compared with 6.8 months for lapatinib-capecitabine (hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .0001).

The PFS benefit was consistently observed across all predefined subgroups, including by trastuzumab resistance.

In trastuzumab-resistant patients, the median PFS was 12.5 months for the pyrotinib combination and 6.9 months for the lapatinib combination (HR, 0.60; 95% CI, 0.29-1.21). In patients without trastuzumab resistance, the median PFS was 12.5 months and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21-0.51).

Although overall survival (OS) data were not yet mature, there was a “strong trend” toward a benefit with pyrotinib, Dr. Xu said. The 12-month OS rate was 91.3% for the pyrotinib combination and 77.4% for lapatinib. The median OS was not reached in either arm at the time of analysis.

Treatment-related adverse events of grade 3 or greater occurred in 57.5% of the pyrotinib arm and 34.1% of the lapatinib arm.

Diarrhea was the most common grade 3 or greater treatment-related adverse event, occurring in 30.6% of patients in the pyrotinib arm and 8.3% of those in the lapatinib arm. No grade 4 or 5 diarrhea was seen.

Overall, diarrhea occurred in 94.8% of patients in the pyrotinib arm and 62.1% of those in the lapatinib arm. However, pyrotinib-associated diarrhea was generally of low severity, occurred early, had a short duration, was reversible, and did not lead to treatment termination, according to Dr. Xu.

This study was funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Xu reported additional disclosures related to AstraZeneca, Eisai, Pfizer, and Roche. Dr. Prat disclosed relationships with Amgen, Daiichi Sankyo, Lilly, MSD Oncology, and other companies.

SOURCE: Xu B et al. ASCO 2020, Abstract 1003

The combination of pyrotinib and capecitabine significantly prolonged progression-free survival (PFS), when compared with lapatinib and capecitabine, among patients with previously treated HER2-positive metastatic breast cancer in a phase 3 trial.

PFS was extended by nearly 6 months among patients who received pyrotinib, a novel pan-HER2 inhibitor, combined with capecitabine. Grade 3 diarrhea occurred in nearly 31% of patients receiving the pyrotinib-capecitabine combination, though none of the patients discontinued treatment due to this adverse event.

Binghe Xu, MD, PhD, of the National Cancer Center/Cancer Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, presented these results, from the phase 3 PHOEBE trial, as part of the American Society of Clinical Oncology virtual scientific program.
 

The value of pyrotinib

Although there are already many targeted therapies for HER2-positive metastatic breast cancer, accessibility can be an issue, with drugs such as pertuzumab and trastuzumab emtansine (T-DM1) not available in all regions of the world, according to Dr. Xu.

“Before we initiated this clinical trial, lapatinib plus capecitabine was the only second-line standard of care against HER2-positive metastatic breast cancer in China,” he said.

Based, in part, on results of the PHOEBE trial, the combination of pyrotinib and capecitabine was approved in China as a second-line standard of care for patients with HER2-positive metastatic breast cancer, according to Dr. Xu.

Pyrotinib has now demonstrated “clinical value” in two phase 3 clinical trials, but its value in relation to pertuzumab, T-DM1, tucatinib, trastuzumab deruxtecan, or neratinib is less clear, said Aleix Prat, MD, PhD, of Hospital Clinic of Barcelona.

“Also, in my opinion, the toxicity profile needs attention,” Dr. Prat said in a discussion of the PHOEBE results that was also part of the virtual ASCO meeting.

The 31% incidence of grade 3 diarrhea was “very similar,” he said, to what was seen in PHENIX, another phase 3 trial of pyrotinib plus capecitabine that was presented at the 2019 ASCO annual meeting (J Clin Oncol 37, 2019 suppl; abstr 1001).

“What is the current therapy landscape? In my opinion, today, the first line remains taxane, trastuzumab, and pertuzumab; the second line T-DM1; and the third line tucatinib, trastuzumab, and capecitabine, with other treatment strategies reserved for later lines,” Dr. Prat said.

Study details

PHOEBE included 267 patients with HER2-positive metastatic breast cancer. They had previously received trastuzumab and taxanes, and/or anthracyclines, with up to two prior lines of chemotherapy for metastatic disease.

The patients’ median age was 50 years, 79% had visceral metastases at screening, and about 26% had trastuzumab resistance, Dr. Xu said. Resistance was defined as relapse within 6 months after adjuvant treatment or progression within 3 months of treatment for metastatic disease.

A statistically significant and clinically meaningful improvement was seen in PFS, the primary endpoint of the study, Dr. Xu said.

Median PFS by blinded independent central review was 12.5 months for the pyrotinib-capecitabine combination, compared with 6.8 months for lapatinib-capecitabine (hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .0001).

The PFS benefit was consistently observed across all predefined subgroups, including by trastuzumab resistance.

In trastuzumab-resistant patients, the median PFS was 12.5 months for the pyrotinib combination and 6.9 months for the lapatinib combination (HR, 0.60; 95% CI, 0.29-1.21). In patients without trastuzumab resistance, the median PFS was 12.5 months and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21-0.51).

Although overall survival (OS) data were not yet mature, there was a “strong trend” toward a benefit with pyrotinib, Dr. Xu said. The 12-month OS rate was 91.3% for the pyrotinib combination and 77.4% for lapatinib. The median OS was not reached in either arm at the time of analysis.

Treatment-related adverse events of grade 3 or greater occurred in 57.5% of the pyrotinib arm and 34.1% of the lapatinib arm.

Diarrhea was the most common grade 3 or greater treatment-related adverse event, occurring in 30.6% of patients in the pyrotinib arm and 8.3% of those in the lapatinib arm. No grade 4 or 5 diarrhea was seen.

Overall, diarrhea occurred in 94.8% of patients in the pyrotinib arm and 62.1% of those in the lapatinib arm. However, pyrotinib-associated diarrhea was generally of low severity, occurred early, had a short duration, was reversible, and did not lead to treatment termination, according to Dr. Xu.

This study was funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Xu reported additional disclosures related to AstraZeneca, Eisai, Pfizer, and Roche. Dr. Prat disclosed relationships with Amgen, Daiichi Sankyo, Lilly, MSD Oncology, and other companies.

SOURCE: Xu B et al. ASCO 2020, Abstract 1003

The combination of pyrotinib and capecitabine significantly prolonged progression-free survival (PFS), when compared with lapatinib and capecitabine, among patients with previously treated HER2-positive metastatic breast cancer in a phase 3 trial.

PFS was extended by nearly 6 months among patients who received pyrotinib, a novel pan-HER2 inhibitor, combined with capecitabine. Grade 3 diarrhea occurred in nearly 31% of patients receiving the pyrotinib-capecitabine combination, though none of the patients discontinued treatment due to this adverse event.

Binghe Xu, MD, PhD, of the National Cancer Center/Cancer Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, presented these results, from the phase 3 PHOEBE trial, as part of the American Society of Clinical Oncology virtual scientific program.
 

The value of pyrotinib

Although there are already many targeted therapies for HER2-positive metastatic breast cancer, accessibility can be an issue, with drugs such as pertuzumab and trastuzumab emtansine (T-DM1) not available in all regions of the world, according to Dr. Xu.

“Before we initiated this clinical trial, lapatinib plus capecitabine was the only second-line standard of care against HER2-positive metastatic breast cancer in China,” he said.

Based, in part, on results of the PHOEBE trial, the combination of pyrotinib and capecitabine was approved in China as a second-line standard of care for patients with HER2-positive metastatic breast cancer, according to Dr. Xu.

Pyrotinib has now demonstrated “clinical value” in two phase 3 clinical trials, but its value in relation to pertuzumab, T-DM1, tucatinib, trastuzumab deruxtecan, or neratinib is less clear, said Aleix Prat, MD, PhD, of Hospital Clinic of Barcelona.

“Also, in my opinion, the toxicity profile needs attention,” Dr. Prat said in a discussion of the PHOEBE results that was also part of the virtual ASCO meeting.

The 31% incidence of grade 3 diarrhea was “very similar,” he said, to what was seen in PHENIX, another phase 3 trial of pyrotinib plus capecitabine that was presented at the 2019 ASCO annual meeting (J Clin Oncol 37, 2019 suppl; abstr 1001).

“What is the current therapy landscape? In my opinion, today, the first line remains taxane, trastuzumab, and pertuzumab; the second line T-DM1; and the third line tucatinib, trastuzumab, and capecitabine, with other treatment strategies reserved for later lines,” Dr. Prat said.

Study details

PHOEBE included 267 patients with HER2-positive metastatic breast cancer. They had previously received trastuzumab and taxanes, and/or anthracyclines, with up to two prior lines of chemotherapy for metastatic disease.

The patients’ median age was 50 years, 79% had visceral metastases at screening, and about 26% had trastuzumab resistance, Dr. Xu said. Resistance was defined as relapse within 6 months after adjuvant treatment or progression within 3 months of treatment for metastatic disease.

A statistically significant and clinically meaningful improvement was seen in PFS, the primary endpoint of the study, Dr. Xu said.

Median PFS by blinded independent central review was 12.5 months for the pyrotinib-capecitabine combination, compared with 6.8 months for lapatinib-capecitabine (hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .0001).

The PFS benefit was consistently observed across all predefined subgroups, including by trastuzumab resistance.

In trastuzumab-resistant patients, the median PFS was 12.5 months for the pyrotinib combination and 6.9 months for the lapatinib combination (HR, 0.60; 95% CI, 0.29-1.21). In patients without trastuzumab resistance, the median PFS was 12.5 months and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21-0.51).

Although overall survival (OS) data were not yet mature, there was a “strong trend” toward a benefit with pyrotinib, Dr. Xu said. The 12-month OS rate was 91.3% for the pyrotinib combination and 77.4% for lapatinib. The median OS was not reached in either arm at the time of analysis.

Treatment-related adverse events of grade 3 or greater occurred in 57.5% of the pyrotinib arm and 34.1% of the lapatinib arm.

Diarrhea was the most common grade 3 or greater treatment-related adverse event, occurring in 30.6% of patients in the pyrotinib arm and 8.3% of those in the lapatinib arm. No grade 4 or 5 diarrhea was seen.

Overall, diarrhea occurred in 94.8% of patients in the pyrotinib arm and 62.1% of those in the lapatinib arm. However, pyrotinib-associated diarrhea was generally of low severity, occurred early, had a short duration, was reversible, and did not lead to treatment termination, according to Dr. Xu.

This study was funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Xu reported additional disclosures related to AstraZeneca, Eisai, Pfizer, and Roche. Dr. Prat disclosed relationships with Amgen, Daiichi Sankyo, Lilly, MSD Oncology, and other companies.

SOURCE: Xu B et al. ASCO 2020, Abstract 1003

A new consensus statement recommends monitoring antipsychotic blood levels, also known as therapeutic drug monitoring (TDM), to inform treatment decisions and optimize safety and efficacy.

The statement, jointly authored by experts from the American Society of Clinical Psychopharmacology (ASCP) and the Germany-based Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie, recommends antipsychotic TDM, particularly for specific patient groups and for patients with suspected nonadherence.

“This [TDM] is a valuable and reliable instrument for personalizing treatment, which is an increasing focus today – individualizing and tailoring pharmacotherapy,” lead author Georgios Schoretsanitis, MD, PhD, department of psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, and Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, said in an interview.

“I am particularly satisfied to say that this paper adds much knowledge and is a holistic approach, focusing not only on theoretical knowledge but also aiming to make the life of clinicians easier, providing more of an algorithm and decision-making instrument for clinical use in everyday clinical scenarios and problems related to antipsychotic treatment,” he added.

The study was published online May 19 in the Journal of Clinical Psychiatry.

Problem-solving tool

“The therapeutic reference range for antipsychotic levels in blood consists of a lower limit, below which therapeutic response is relatively unlikely, and an upper limit, above which ADRs [adverse drug reactions] … are more likely to occur,” the authors wrote.

TDM can determine whether a patient has a subtherapeutic antipsychotic blood concentration and may explain a lack of response or a supra-therapeutic concentration, which could be associated with adverse drug reactions.

“It is important for clinicians to realize that this type of monitoring is not equally indicated for all antipsychotics and not planned as a way of providing insight if there are no questions. In other words, it is a problem-solving tool for a problem, a complicated situation, or a challenging scenario you’re trying to solve,” Dr. Schoretsanitis said.

The authors divided their recommendations regarding routine TDM for antipsychotics into four categories, based on level of evidence:

Strongly recommended (Level 1)

• Clozapine
• Fluphenazine
• Haloperidol
• Olanzapine
• Perazine
• Perphenazine

Recommended (Level 2)

• Aripiprazole
• Chlorpromazine
• Flupentixol
• Paliperidone
• Quetiapine
• Risperidone
• Sertindole
• Ziprasidone

Useful (Level 3)

• Brexpiprazole
• Cariprazine
• Chlorprothixene
• Iloperidone
• Loxapine
• Lurasidone
• Melperone
• Pimozide

Potentially useful (Level 4)

• Asenapine

“We tried to narrow down specific situations and scenarios in which TDM can be useful and, in fact, has proven benefits,” said Dr. Schoretsanitis.

Patients who have no clinical response, even within established dose ranges, who have a recurrence or relapse during maintenance treatment, or who have ADRs are candidates for TDM.

Patients receiving polypharmacy can benefit from TDM because some coprescribed medications can raise or lower antipsychotic blood levels via overlapping metabolic pathways.

Additional populations requiring TDM are elderly patients, pregnant/lactating women, patients with medical comorbidities such as renal or hepatic disease, children/adolescents, patients with intellectual disabilities, and forensic or court-mandated patients.

Dr. Schoretsanitis noted that switching between formulations – for example from an oral to a long-acting injectable antipsychotic (LAI) – can “easily be guided by regular use of TDM,” as can switching from a brand name drug to a generic.

Patients with acute inflammatory conditions, such as COVID-19, “are good candidates for TDM, even with drugs that were previously well-tolerated, because inflammation affects the way the body metabolizes drugs, leaving patients at high risk for developing toxicity,” he added.

“The most common scenario for using TDM in clinical practice is to measure adherence to antipsychotics, since TDM is one of the most reliable ways to assess adherence and thereby prevent relapse or recurrence of the disease,” said Dr. Schoretsanitis.
 

Long overdue

Sheldon Preskorn, MD, professor of psychiatry, University of Kansas, Wichita, and chief science officer for KUSM-W Clinical Trials Unit, said in an interview that drawing blood 24 hours after taking the drug can help determine the patient’s clearance of the drug.

“If the level is too low, either the patient is not taking the drug at all, or is taking too little, or is a rapid metabolizer, so the dose may have to be adjusted,” said Dr. Preskorn, who was not involved in developing the consensus statement.

This is also an opportunity to initiate a conversation with patients regarding adherence, explaining that a low blood level will not have a therapeutic effect, discussing whether the patient has been taking the medication as prescribed, and addressing reasons for nonadherence, said Dr. Preskorn.

“We want to make it clear that clinicians should treat the patient, not the blood level,” said Dr. Schoretsanitis.

“If a person is tolerating and responding to medications well, but we measure and see something unexpected, such as low levels, this doesn’t mean we need to adjust the dose merely because the levels are low,” he added.

“Timing is very important” when measuring blood levels. For example, if a patient’s blood is usually tested in the morning but then is tested in the afternoon, he or she may exhibit a lower blood level, which may be reflective of the timing of the test rather than drug response.

“This statement is long overdue because TDM is probably the most underutilized tool in psychiatry for individualizing pharmacotherapy,” said Dr. Preskorn.

Also commenting on the consensus statement, Jonathan Meyer, MD, clinical professor of psychiatry, University of California, San Diego, said it brings attention to some of the key issues associated with antipsychotic plasma monitoring and shows TDM is a valuable decision-making tool.

Dr. Meyer, who was not involved in developing the document, pointed out that it may be difficult to obtain levels on newer antipsychotics, which require specialized labs that are not widely available and sometimes take up to 2 weeks to get results.

In such cases, physicians will have to rely on their best clinical judgment to manage an inadequate response until TDM results are available.

No commercial organizations had any role in funding the statement. Dr. Schoretsanitis has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Meyer reports having received speaking or advising fees in the prior 12 months from Acadia Pharmaceuticals, Alkermes, Allergan (now AbbVie), Intra-Cellular Therapies, Janssen Pharmaceutica, Neurocrine, Otsuka America Inc., Sunovion Pharmaceuticals, and Teva Pharmaceutical Industries Ltd. Dr. Preskorn reports having been an investigator and/or a consultant to more than 140 pharmaceutical, biotechnology, diagnostic, and device companies and to the Food and Drug Administration and other federal agencies.
 

A version of this article originally appeared on Medscape.com.

A new consensus statement recommends monitoring antipsychotic blood levels, also known as therapeutic drug monitoring (TDM), to inform treatment decisions and optimize safety and efficacy.

The statement, jointly authored by experts from the American Society of Clinical Psychopharmacology (ASCP) and the Germany-based Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie, recommends antipsychotic TDM, particularly for specific patient groups and for patients with suspected nonadherence.

“This [TDM] is a valuable and reliable instrument for personalizing treatment, which is an increasing focus today – individualizing and tailoring pharmacotherapy,” lead author Georgios Schoretsanitis, MD, PhD, department of psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, and Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, said in an interview.

“I am particularly satisfied to say that this paper adds much knowledge and is a holistic approach, focusing not only on theoretical knowledge but also aiming to make the life of clinicians easier, providing more of an algorithm and decision-making instrument for clinical use in everyday clinical scenarios and problems related to antipsychotic treatment,” he added.

The study was published online May 19 in the Journal of Clinical Psychiatry.

Problem-solving tool

“The therapeutic reference range for antipsychotic levels in blood consists of a lower limit, below which therapeutic response is relatively unlikely, and an upper limit, above which ADRs [adverse drug reactions] … are more likely to occur,” the authors wrote.

TDM can determine whether a patient has a subtherapeutic antipsychotic blood concentration and may explain a lack of response or a supra-therapeutic concentration, which could be associated with adverse drug reactions.

“It is important for clinicians to realize that this type of monitoring is not equally indicated for all antipsychotics and not planned as a way of providing insight if there are no questions. In other words, it is a problem-solving tool for a problem, a complicated situation, or a challenging scenario you’re trying to solve,” Dr. Schoretsanitis said.

The authors divided their recommendations regarding routine TDM for antipsychotics into four categories, based on level of evidence:

Strongly recommended (Level 1)

• Clozapine
• Fluphenazine
• Haloperidol
• Olanzapine
• Perazine
• Perphenazine

Recommended (Level 2)

• Aripiprazole
• Chlorpromazine
• Flupentixol
• Paliperidone
• Quetiapine
• Risperidone
• Sertindole
• Ziprasidone

Useful (Level 3)

• Brexpiprazole
• Cariprazine
• Chlorprothixene
• Iloperidone
• Loxapine
• Lurasidone
• Melperone
• Pimozide

Potentially useful (Level 4)

• Asenapine

“We tried to narrow down specific situations and scenarios in which TDM can be useful and, in fact, has proven benefits,” said Dr. Schoretsanitis.

Patients who have no clinical response, even within established dose ranges, who have a recurrence or relapse during maintenance treatment, or who have ADRs are candidates for TDM.

Patients receiving polypharmacy can benefit from TDM because some coprescribed medications can raise or lower antipsychotic blood levels via overlapping metabolic pathways.

Additional populations requiring TDM are elderly patients, pregnant/lactating women, patients with medical comorbidities such as renal or hepatic disease, children/adolescents, patients with intellectual disabilities, and forensic or court-mandated patients.

Dr. Schoretsanitis noted that switching between formulations – for example from an oral to a long-acting injectable antipsychotic (LAI) – can “easily be guided by regular use of TDM,” as can switching from a brand name drug to a generic.

Patients with acute inflammatory conditions, such as COVID-19, “are good candidates for TDM, even with drugs that were previously well-tolerated, because inflammation affects the way the body metabolizes drugs, leaving patients at high risk for developing toxicity,” he added.

“The most common scenario for using TDM in clinical practice is to measure adherence to antipsychotics, since TDM is one of the most reliable ways to assess adherence and thereby prevent relapse or recurrence of the disease,” said Dr. Schoretsanitis.
 

Long overdue

Sheldon Preskorn, MD, professor of psychiatry, University of Kansas, Wichita, and chief science officer for KUSM-W Clinical Trials Unit, said in an interview that drawing blood 24 hours after taking the drug can help determine the patient’s clearance of the drug.

“If the level is too low, either the patient is not taking the drug at all, or is taking too little, or is a rapid metabolizer, so the dose may have to be adjusted,” said Dr. Preskorn, who was not involved in developing the consensus statement.

This is also an opportunity to initiate a conversation with patients regarding adherence, explaining that a low blood level will not have a therapeutic effect, discussing whether the patient has been taking the medication as prescribed, and addressing reasons for nonadherence, said Dr. Preskorn.

“We want to make it clear that clinicians should treat the patient, not the blood level,” said Dr. Schoretsanitis.

“If a person is tolerating and responding to medications well, but we measure and see something unexpected, such as low levels, this doesn’t mean we need to adjust the dose merely because the levels are low,” he added.

“Timing is very important” when measuring blood levels. For example, if a patient’s blood is usually tested in the morning but then is tested in the afternoon, he or she may exhibit a lower blood level, which may be reflective of the timing of the test rather than drug response.

“This statement is long overdue because TDM is probably the most underutilized tool in psychiatry for individualizing pharmacotherapy,” said Dr. Preskorn.

Also commenting on the consensus statement, Jonathan Meyer, MD, clinical professor of psychiatry, University of California, San Diego, said it brings attention to some of the key issues associated with antipsychotic plasma monitoring and shows TDM is a valuable decision-making tool.

Dr. Meyer, who was not involved in developing the document, pointed out that it may be difficult to obtain levels on newer antipsychotics, which require specialized labs that are not widely available and sometimes take up to 2 weeks to get results.

In such cases, physicians will have to rely on their best clinical judgment to manage an inadequate response until TDM results are available.

No commercial organizations had any role in funding the statement. Dr. Schoretsanitis has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Meyer reports having received speaking or advising fees in the prior 12 months from Acadia Pharmaceuticals, Alkermes, Allergan (now AbbVie), Intra-Cellular Therapies, Janssen Pharmaceutica, Neurocrine, Otsuka America Inc., Sunovion Pharmaceuticals, and Teva Pharmaceutical Industries Ltd. Dr. Preskorn reports having been an investigator and/or a consultant to more than 140 pharmaceutical, biotechnology, diagnostic, and device companies and to the Food and Drug Administration and other federal agencies.
 

A version of this article originally appeared on Medscape.com.

A new consensus statement recommends monitoring antipsychotic blood levels, also known as therapeutic drug monitoring (TDM), to inform treatment decisions and optimize safety and efficacy.

The statement, jointly authored by experts from the American Society of Clinical Psychopharmacology (ASCP) and the Germany-based Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie, recommends antipsychotic TDM, particularly for specific patient groups and for patients with suspected nonadherence.

“This [TDM] is a valuable and reliable instrument for personalizing treatment, which is an increasing focus today – individualizing and tailoring pharmacotherapy,” lead author Georgios Schoretsanitis, MD, PhD, department of psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, and Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, said in an interview.

“I am particularly satisfied to say that this paper adds much knowledge and is a holistic approach, focusing not only on theoretical knowledge but also aiming to make the life of clinicians easier, providing more of an algorithm and decision-making instrument for clinical use in everyday clinical scenarios and problems related to antipsychotic treatment,” he added.

The study was published online May 19 in the Journal of Clinical Psychiatry.

Problem-solving tool

“The therapeutic reference range for antipsychotic levels in blood consists of a lower limit, below which therapeutic response is relatively unlikely, and an upper limit, above which ADRs [adverse drug reactions] … are more likely to occur,” the authors wrote.

TDM can determine whether a patient has a subtherapeutic antipsychotic blood concentration and may explain a lack of response or a supra-therapeutic concentration, which could be associated with adverse drug reactions.

“It is important for clinicians to realize that this type of monitoring is not equally indicated for all antipsychotics and not planned as a way of providing insight if there are no questions. In other words, it is a problem-solving tool for a problem, a complicated situation, or a challenging scenario you’re trying to solve,” Dr. Schoretsanitis said.

The authors divided their recommendations regarding routine TDM for antipsychotics into four categories, based on level of evidence:

Strongly recommended (Level 1)

• Clozapine
• Fluphenazine
• Haloperidol
• Olanzapine
• Perazine
• Perphenazine

Recommended (Level 2)

• Aripiprazole
• Chlorpromazine
• Flupentixol
• Paliperidone
• Quetiapine
• Risperidone
• Sertindole
• Ziprasidone

Useful (Level 3)

• Brexpiprazole
• Cariprazine
• Chlorprothixene
• Iloperidone
• Loxapine
• Lurasidone
• Melperone
• Pimozide

Potentially useful (Level 4)

• Asenapine

“We tried to narrow down specific situations and scenarios in which TDM can be useful and, in fact, has proven benefits,” said Dr. Schoretsanitis.

Patients who have no clinical response, even within established dose ranges, who have a recurrence or relapse during maintenance treatment, or who have ADRs are candidates for TDM.

Patients receiving polypharmacy can benefit from TDM because some coprescribed medications can raise or lower antipsychotic blood levels via overlapping metabolic pathways.

Additional populations requiring TDM are elderly patients, pregnant/lactating women, patients with medical comorbidities such as renal or hepatic disease, children/adolescents, patients with intellectual disabilities, and forensic or court-mandated patients.

Dr. Schoretsanitis noted that switching between formulations – for example from an oral to a long-acting injectable antipsychotic (LAI) – can “easily be guided by regular use of TDM,” as can switching from a brand name drug to a generic.

Patients with acute inflammatory conditions, such as COVID-19, “are good candidates for TDM, even with drugs that were previously well-tolerated, because inflammation affects the way the body metabolizes drugs, leaving patients at high risk for developing toxicity,” he added.

“The most common scenario for using TDM in clinical practice is to measure adherence to antipsychotics, since TDM is one of the most reliable ways to assess adherence and thereby prevent relapse or recurrence of the disease,” said Dr. Schoretsanitis.
 

Long overdue

Sheldon Preskorn, MD, professor of psychiatry, University of Kansas, Wichita, and chief science officer for KUSM-W Clinical Trials Unit, said in an interview that drawing blood 24 hours after taking the drug can help determine the patient’s clearance of the drug.

“If the level is too low, either the patient is not taking the drug at all, or is taking too little, or is a rapid metabolizer, so the dose may have to be adjusted,” said Dr. Preskorn, who was not involved in developing the consensus statement.

This is also an opportunity to initiate a conversation with patients regarding adherence, explaining that a low blood level will not have a therapeutic effect, discussing whether the patient has been taking the medication as prescribed, and addressing reasons for nonadherence, said Dr. Preskorn.

“We want to make it clear that clinicians should treat the patient, not the blood level,” said Dr. Schoretsanitis.

“If a person is tolerating and responding to medications well, but we measure and see something unexpected, such as low levels, this doesn’t mean we need to adjust the dose merely because the levels are low,” he added.

“Timing is very important” when measuring blood levels. For example, if a patient’s blood is usually tested in the morning but then is tested in the afternoon, he or she may exhibit a lower blood level, which may be reflective of the timing of the test rather than drug response.

“This statement is long overdue because TDM is probably the most underutilized tool in psychiatry for individualizing pharmacotherapy,” said Dr. Preskorn.

Also commenting on the consensus statement, Jonathan Meyer, MD, clinical professor of psychiatry, University of California, San Diego, said it brings attention to some of the key issues associated with antipsychotic plasma monitoring and shows TDM is a valuable decision-making tool.

Dr. Meyer, who was not involved in developing the document, pointed out that it may be difficult to obtain levels on newer antipsychotics, which require specialized labs that are not widely available and sometimes take up to 2 weeks to get results.

In such cases, physicians will have to rely on their best clinical judgment to manage an inadequate response until TDM results are available.

No commercial organizations had any role in funding the statement. Dr. Schoretsanitis has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Meyer reports having received speaking or advising fees in the prior 12 months from Acadia Pharmaceuticals, Alkermes, Allergan (now AbbVie), Intra-Cellular Therapies, Janssen Pharmaceutica, Neurocrine, Otsuka America Inc., Sunovion Pharmaceuticals, and Teva Pharmaceutical Industries Ltd. Dr. Preskorn reports having been an investigator and/or a consultant to more than 140 pharmaceutical, biotechnology, diagnostic, and device companies and to the Food and Drug Administration and other federal agencies.
 

A version of this article originally appeared on Medscape.com.

For patients with BRCA-like triple-negative breast cancer (TNBC), adding veliparib to cisplatin chemotherapy may extend survival, based on results from the phase 3 SWOG S1416 trial.

All patients with BRCA-like TNBC had a significant improvement in progression-free survival (PFS) when they received veliparib plus cisplatin. Previously untreated patients with BRCA-like TNBC had a significant improvement in overall survival (OS) as well.

The results are a “very positive step towards expanding the role of PARP inhibitors beyond germline BRCA in breast cancer,” reported lead author Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

According to Dr. Sharma, PARP inhibitors have demonstrated efficacy for certain patients with BRCA wild-type ovarian cancer, such as those with homologous recombination deficiency, which also occurs in approximately half of patients with BRCA wild-type TNBC. In TNBC, homologous recombination deficiency and other aberrations lead to a BRCA-like disease phenotype, which may respond to PARP inhibitors.

Dr. Sharma noted that previous attempts to use PARP inhibitors for BRCA wild-type TNBC have revealed obstacles, such as the inefficacy of PARP inhibitor monotherapy and dose-limiting myelosuppression when PARP inhibitors were added to chemotherapy. The issue of bone marrow toxicity may be mitigated by veliparib, which has minimal PARP-trapping activity, she explained.

“A phase 1 trial has demonstrated that adequate doses of cisplatin can be delivered safely in combination with the near-maximal single-agent dose of veliparib in patients with metastatic TNBC,” Dr. Sharma said.

She and her colleagues put this finding to the test in a phase 3 trial that enrolled 335 patients with metastatic and/or loco-regionally recurrent TNBC or BRCA-associated HER2-negative breast cancer. Patients could be previously untreated or have received one prior cytotoxic chemotherapy for metastatic disease.

Of the patients enrolled, 321 met eligibility criteria, 294 had germline BRCA testing, and 209 had BRCA-like assessment.

Patients were divided into the following groups: germline BRCA-associated disease (n = 37), BRCA-like disease (n = 99), non-BRCA-like disease (n = 110), and unclassified (n = 75).

In each group, patients were randomized in a 1:1 ratio to receive cisplatin (75 mg/m²on day 1) plus veliparib (300 mg twice daily on days 1-14) every 3 weeks, or cisplatin with placebo. The primary endpoint was PFS.

Results

Among patients with BRCA-like disease, there was a significant improvement in PFS and a trend toward improved OS when veliparib was added to cisplatin. The median PFS was 5.9 months with veliparib and 4.2 months with placebo (P = .006). The median OS was 14.0 months and 12.1 months, respectively (P = .067).

Among patients with previously untreated BRCA-like disease, there were significant improvements in both PFS and OS.

The median PFS in this group was 6.1 months with veliparib and 4.2 months with placebo (P = .008). The 12-month PFS rates were 23% and 3%, respectively.

The median OS in this group was 17.8 months with veliparib and 10.3 months with placebo (P = .048). The 24-month OS rates were 43% and 20%, respectively.

There were no survival benefits with veliparib among patients with unclassified disease, non-BRCA-like disease, or BRCA-associated disease.

Dr. Sharma noted that the lack of significant improvement in the BRCA-associated group was likely due to the small sample size. “FDA approval of PARP inhibitors for treatment of germline BRCA-associated metastatic breast cancer during the course of this trial impacted accrual to this group,” she said.

Veliparib was associated with a higher rate of grade 3-4 hematologic toxicities, including neutropenia (46% vs. 19%), leukopenia (27% vs. 7%), anemia (23% vs. 7%), and thrombocytopenia (19% vs. 3%).

Dr. Sharma said results from this trial should prompt further research. “The combination of veliparib plus cisplatin warrants further evaluation in larger randomized trials for patients with BRCA-like phenotype TNBC,” she said.

Invited discussant Catherine M. Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, called the trial “an ambitious study” that has created a “valuable tissue bank” for future translational research. She agreed that more work is necessary.

“Further research is needed to identify the optimal homologous recombination deficiency biomarkers critical in the early treatment-naive and in the advanced treatment-exposed disease settings,” Dr. Kelly said.

SWOG S1416 was funded by the National Institutes of Health and AbbVie. Dr. Sharma disclosed relationships with AstraZeneca, Merck, Novartis, and other companies. Dr. Kelly reported affiliations with Pfizer, Novartis, Roche, and MSD Oncology.

SOURCE: Sharma et al. ASCO 2020, Abstract 1001.

For patients with BRCA-like triple-negative breast cancer (TNBC), adding veliparib to cisplatin chemotherapy may extend survival, based on results from the phase 3 SWOG S1416 trial.

All patients with BRCA-like TNBC had a significant improvement in progression-free survival (PFS) when they received veliparib plus cisplatin. Previously untreated patients with BRCA-like TNBC had a significant improvement in overall survival (OS) as well.

The results are a “very positive step towards expanding the role of PARP inhibitors beyond germline BRCA in breast cancer,” reported lead author Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

According to Dr. Sharma, PARP inhibitors have demonstrated efficacy for certain patients with BRCA wild-type ovarian cancer, such as those with homologous recombination deficiency, which also occurs in approximately half of patients with BRCA wild-type TNBC. In TNBC, homologous recombination deficiency and other aberrations lead to a BRCA-like disease phenotype, which may respond to PARP inhibitors.

Dr. Sharma noted that previous attempts to use PARP inhibitors for BRCA wild-type TNBC have revealed obstacles, such as the inefficacy of PARP inhibitor monotherapy and dose-limiting myelosuppression when PARP inhibitors were added to chemotherapy. The issue of bone marrow toxicity may be mitigated by veliparib, which has minimal PARP-trapping activity, she explained.

“A phase 1 trial has demonstrated that adequate doses of cisplatin can be delivered safely in combination with the near-maximal single-agent dose of veliparib in patients with metastatic TNBC,” Dr. Sharma said.

She and her colleagues put this finding to the test in a phase 3 trial that enrolled 335 patients with metastatic and/or loco-regionally recurrent TNBC or BRCA-associated HER2-negative breast cancer. Patients could be previously untreated or have received one prior cytotoxic chemotherapy for metastatic disease.

Of the patients enrolled, 321 met eligibility criteria, 294 had germline BRCA testing, and 209 had BRCA-like assessment.

Patients were divided into the following groups: germline BRCA-associated disease (n = 37), BRCA-like disease (n = 99), non-BRCA-like disease (n = 110), and unclassified (n = 75).

In each group, patients were randomized in a 1:1 ratio to receive cisplatin (75 mg/m²on day 1) plus veliparib (300 mg twice daily on days 1-14) every 3 weeks, or cisplatin with placebo. The primary endpoint was PFS.

Results

Among patients with BRCA-like disease, there was a significant improvement in PFS and a trend toward improved OS when veliparib was added to cisplatin. The median PFS was 5.9 months with veliparib and 4.2 months with placebo (P = .006). The median OS was 14.0 months and 12.1 months, respectively (P = .067).

Among patients with previously untreated BRCA-like disease, there were significant improvements in both PFS and OS.

The median PFS in this group was 6.1 months with veliparib and 4.2 months with placebo (P = .008). The 12-month PFS rates were 23% and 3%, respectively.

The median OS in this group was 17.8 months with veliparib and 10.3 months with placebo (P = .048). The 24-month OS rates were 43% and 20%, respectively.

There were no survival benefits with veliparib among patients with unclassified disease, non-BRCA-like disease, or BRCA-associated disease.

Dr. Sharma noted that the lack of significant improvement in the BRCA-associated group was likely due to the small sample size. “FDA approval of PARP inhibitors for treatment of germline BRCA-associated metastatic breast cancer during the course of this trial impacted accrual to this group,” she said.

Veliparib was associated with a higher rate of grade 3-4 hematologic toxicities, including neutropenia (46% vs. 19%), leukopenia (27% vs. 7%), anemia (23% vs. 7%), and thrombocytopenia (19% vs. 3%).

Dr. Sharma said results from this trial should prompt further research. “The combination of veliparib plus cisplatin warrants further evaluation in larger randomized trials for patients with BRCA-like phenotype TNBC,” she said.

Invited discussant Catherine M. Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, called the trial “an ambitious study” that has created a “valuable tissue bank” for future translational research. She agreed that more work is necessary.

“Further research is needed to identify the optimal homologous recombination deficiency biomarkers critical in the early treatment-naive and in the advanced treatment-exposed disease settings,” Dr. Kelly said.

SWOG S1416 was funded by the National Institutes of Health and AbbVie. Dr. Sharma disclosed relationships with AstraZeneca, Merck, Novartis, and other companies. Dr. Kelly reported affiliations with Pfizer, Novartis, Roche, and MSD Oncology.

SOURCE: Sharma et al. ASCO 2020, Abstract 1001.

For patients with BRCA-like triple-negative breast cancer (TNBC), adding veliparib to cisplatin chemotherapy may extend survival, based on results from the phase 3 SWOG S1416 trial.

All patients with BRCA-like TNBC had a significant improvement in progression-free survival (PFS) when they received veliparib plus cisplatin. Previously untreated patients with BRCA-like TNBC had a significant improvement in overall survival (OS) as well.

The results are a “very positive step towards expanding the role of PARP inhibitors beyond germline BRCA in breast cancer,” reported lead author Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

According to Dr. Sharma, PARP inhibitors have demonstrated efficacy for certain patients with BRCA wild-type ovarian cancer, such as those with homologous recombination deficiency, which also occurs in approximately half of patients with BRCA wild-type TNBC. In TNBC, homologous recombination deficiency and other aberrations lead to a BRCA-like disease phenotype, which may respond to PARP inhibitors.

Dr. Sharma noted that previous attempts to use PARP inhibitors for BRCA wild-type TNBC have revealed obstacles, such as the inefficacy of PARP inhibitor monotherapy and dose-limiting myelosuppression when PARP inhibitors were added to chemotherapy. The issue of bone marrow toxicity may be mitigated by veliparib, which has minimal PARP-trapping activity, she explained.

“A phase 1 trial has demonstrated that adequate doses of cisplatin can be delivered safely in combination with the near-maximal single-agent dose of veliparib in patients with metastatic TNBC,” Dr. Sharma said.

She and her colleagues put this finding to the test in a phase 3 trial that enrolled 335 patients with metastatic and/or loco-regionally recurrent TNBC or BRCA-associated HER2-negative breast cancer. Patients could be previously untreated or have received one prior cytotoxic chemotherapy for metastatic disease.

Of the patients enrolled, 321 met eligibility criteria, 294 had germline BRCA testing, and 209 had BRCA-like assessment.

Patients were divided into the following groups: germline BRCA-associated disease (n = 37), BRCA-like disease (n = 99), non-BRCA-like disease (n = 110), and unclassified (n = 75).

In each group, patients were randomized in a 1:1 ratio to receive cisplatin (75 mg/m²on day 1) plus veliparib (300 mg twice daily on days 1-14) every 3 weeks, or cisplatin with placebo. The primary endpoint was PFS.

Results

Among patients with BRCA-like disease, there was a significant improvement in PFS and a trend toward improved OS when veliparib was added to cisplatin. The median PFS was 5.9 months with veliparib and 4.2 months with placebo (P = .006). The median OS was 14.0 months and 12.1 months, respectively (P = .067).

Among patients with previously untreated BRCA-like disease, there were significant improvements in both PFS and OS.

The median PFS in this group was 6.1 months with veliparib and 4.2 months with placebo (P = .008). The 12-month PFS rates were 23% and 3%, respectively.

The median OS in this group was 17.8 months with veliparib and 10.3 months with placebo (P = .048). The 24-month OS rates were 43% and 20%, respectively.

There were no survival benefits with veliparib among patients with unclassified disease, non-BRCA-like disease, or BRCA-associated disease.

Dr. Sharma noted that the lack of significant improvement in the BRCA-associated group was likely due to the small sample size. “FDA approval of PARP inhibitors for treatment of germline BRCA-associated metastatic breast cancer during the course of this trial impacted accrual to this group,” she said.

Veliparib was associated with a higher rate of grade 3-4 hematologic toxicities, including neutropenia (46% vs. 19%), leukopenia (27% vs. 7%), anemia (23% vs. 7%), and thrombocytopenia (19% vs. 3%).

Dr. Sharma said results from this trial should prompt further research. “The combination of veliparib plus cisplatin warrants further evaluation in larger randomized trials for patients with BRCA-like phenotype TNBC,” she said.

Invited discussant Catherine M. Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, called the trial “an ambitious study” that has created a “valuable tissue bank” for future translational research. She agreed that more work is necessary.

“Further research is needed to identify the optimal homologous recombination deficiency biomarkers critical in the early treatment-naive and in the advanced treatment-exposed disease settings,” Dr. Kelly said.

SWOG S1416 was funded by the National Institutes of Health and AbbVie. Dr. Sharma disclosed relationships with AstraZeneca, Merck, Novartis, and other companies. Dr. Kelly reported affiliations with Pfizer, Novartis, Roche, and MSD Oncology.

SOURCE: Sharma et al. ASCO 2020, Abstract 1001.

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.

Neither fulvestrant alone nor fulvestrant plus anastrozole improved the endocrine-sensitive disease rate (ESDR) versus anastrozole alone as neoadjuvant endocrine therapy in postmenopausal women with locally advanced estrogen receptor-positive HER2-negative (ER+ HER2–) breast cancer in the phase 3 ALTERNATE trial.

The ESDRs were 22.7% in 431 evaluable patients randomized to receive fulvestrant alone, 20.5% in 434 patients who received fulvestrant + anastrozole, and 18.6% in 434 who received anastrozole alone, Cynthia X. Ma, MD, PhD, reported as part of the American Society of Clinical Oncology virtual scientific program.

The differences between the anastrozole-only and the fulvestrant groups did not differ significantly, said Dr. Ma, a professor at Washington University in St. Louis.

Study subjects had a median age of 64 years, clinical stage II/III ER+ HER2– breast cancer, and were randomized 1:1:1 between February 2014 and November 2018 to receive 6 months of treatment with 500 mg of intramuscular fulvestrant given every 4 weeks following a loading dose, fulvestrant plus a 1 mg daily oral does of anastrozole, or anastrozole alone prior to breast conserving surgery.

The groups were similar with respect to baseline characteristics, and more than 70% were eligible for breast conserving surgery prior to the start of neoadjuvant therapy, Dr. Ma noted, adding that the treatments were well tolerated.

Grade 3 or 4 adverse events were rare, and the percentage of patients experiencing arthralgia, myalgia, or hot flashes was low and similar across arms, she said.

“Neoadjuvant therapy downstages the tumor and improves the rate of breast conserving surgery,” Dr. Ma said, adding that pathologic tumor size, nodal status, Ki67 level, and ER status of resected tumors after neoadjuvant therapy have been shown to be independent prognostic factors for relapse-free survival.

sworcester@mdedge.com

SOURCE: Ma C et al. ASCO 2020: Abstract 504.

Neither fulvestrant alone nor fulvestrant plus anastrozole improved the endocrine-sensitive disease rate (ESDR) versus anastrozole alone as neoadjuvant endocrine therapy in postmenopausal women with locally advanced estrogen receptor-positive HER2-negative (ER+ HER2–) breast cancer in the phase 3 ALTERNATE trial.

The ESDRs were 22.7% in 431 evaluable patients randomized to receive fulvestrant alone, 20.5% in 434 patients who received fulvestrant + anastrozole, and 18.6% in 434 who received anastrozole alone, Cynthia X. Ma, MD, PhD, reported as part of the American Society of Clinical Oncology virtual scientific program.

The differences between the anastrozole-only and the fulvestrant groups did not differ significantly, said Dr. Ma, a professor at Washington University in St. Louis.

Study subjects had a median age of 64 years, clinical stage II/III ER+ HER2– breast cancer, and were randomized 1:1:1 between February 2014 and November 2018 to receive 6 months of treatment with 500 mg of intramuscular fulvestrant given every 4 weeks following a loading dose, fulvestrant plus a 1 mg daily oral does of anastrozole, or anastrozole alone prior to breast conserving surgery.

The groups were similar with respect to baseline characteristics, and more than 70% were eligible for breast conserving surgery prior to the start of neoadjuvant therapy, Dr. Ma noted, adding that the treatments were well tolerated.

Grade 3 or 4 adverse events were rare, and the percentage of patients experiencing arthralgia, myalgia, or hot flashes was low and similar across arms, she said.

“Neoadjuvant therapy downstages the tumor and improves the rate of breast conserving surgery,” Dr. Ma said, adding that pathologic tumor size, nodal status, Ki67 level, and ER status of resected tumors after neoadjuvant therapy have been shown to be independent prognostic factors for relapse-free survival.

sworcester@mdedge.com

SOURCE: Ma C et al. ASCO 2020: Abstract 504.

Neither fulvestrant alone nor fulvestrant plus anastrozole improved the endocrine-sensitive disease rate (ESDR) versus anastrozole alone as neoadjuvant endocrine therapy in postmenopausal women with locally advanced estrogen receptor-positive HER2-negative (ER+ HER2–) breast cancer in the phase 3 ALTERNATE trial.

The ESDRs were 22.7% in 431 evaluable patients randomized to receive fulvestrant alone, 20.5% in 434 patients who received fulvestrant + anastrozole, and 18.6% in 434 who received anastrozole alone, Cynthia X. Ma, MD, PhD, reported as part of the American Society of Clinical Oncology virtual scientific program.

The differences between the anastrozole-only and the fulvestrant groups did not differ significantly, said Dr. Ma, a professor at Washington University in St. Louis.

Study subjects had a median age of 64 years, clinical stage II/III ER+ HER2– breast cancer, and were randomized 1:1:1 between February 2014 and November 2018 to receive 6 months of treatment with 500 mg of intramuscular fulvestrant given every 4 weeks following a loading dose, fulvestrant plus a 1 mg daily oral does of anastrozole, or anastrozole alone prior to breast conserving surgery.

The groups were similar with respect to baseline characteristics, and more than 70% were eligible for breast conserving surgery prior to the start of neoadjuvant therapy, Dr. Ma noted, adding that the treatments were well tolerated.

Grade 3 or 4 adverse events were rare, and the percentage of patients experiencing arthralgia, myalgia, or hot flashes was low and similar across arms, she said.

“Neoadjuvant therapy downstages the tumor and improves the rate of breast conserving surgery,” Dr. Ma said, adding that pathologic tumor size, nodal status, Ki67 level, and ER status of resected tumors after neoadjuvant therapy have been shown to be independent prognostic factors for relapse-free survival.

sworcester@mdedge.com

SOURCE: Ma C et al. ASCO 2020: Abstract 504.

Ever since the first picosecond laser hit the market in 2012 as an option for treating unwanted tattoos and pigmented lesions, clinicians have used the technology to safely and effectively treat an expanding range of dermatologic conditions, from Nevus of Ota and melasma to rejuvenation.

In an exhaustive systematic review published online April 13 in Lasers in Surgery and Medicine (2020. doi: 10.1002/lsm.23244), experts from Cosmetic Laser Dermatology in San Diego, Calif., and the Wellman Center for Photomedicine at Massachusetts General Hospital in Boston crafted evidence-based recommendations for using picosecond lasers, which currently feature pulse durations between 300 and 900 picoseconds. They called for further development of the technology and predicted that application of the devices will become more widespread.

dbrunk@mdedge.com

SOURCE: Wu DC et al. Lasers Surg Med. 2020. doi: 10.1002/lsm.23244.

Ever since the first picosecond laser hit the market in 2012 as an option for treating unwanted tattoos and pigmented lesions, clinicians have used the technology to safely and effectively treat an expanding range of dermatologic conditions, from Nevus of Ota and melasma to rejuvenation.

In an exhaustive systematic review published online April 13 in Lasers in Surgery and Medicine (2020. doi: 10.1002/lsm.23244), experts from Cosmetic Laser Dermatology in San Diego, Calif., and the Wellman Center for Photomedicine at Massachusetts General Hospital in Boston crafted evidence-based recommendations for using picosecond lasers, which currently feature pulse durations between 300 and 900 picoseconds. They called for further development of the technology and predicted that application of the devices will become more widespread.

dbrunk@mdedge.com

SOURCE: Wu DC et al. Lasers Surg Med. 2020. doi: 10.1002/lsm.23244.

Ever since the first picosecond laser hit the market in 2012 as an option for treating unwanted tattoos and pigmented lesions, clinicians have used the technology to safely and effectively treat an expanding range of dermatologic conditions, from Nevus of Ota and melasma to rejuvenation.

In an exhaustive systematic review published online April 13 in Lasers in Surgery and Medicine (2020. doi: 10.1002/lsm.23244), experts from Cosmetic Laser Dermatology in San Diego, Calif., and the Wellman Center for Photomedicine at Massachusetts General Hospital in Boston crafted evidence-based recommendations for using picosecond lasers, which currently feature pulse durations between 300 and 900 picoseconds. They called for further development of the technology and predicted that application of the devices will become more widespread.

dbrunk@mdedge.com

SOURCE: Wu DC et al. Lasers Surg Med. 2020. doi: 10.1002/lsm.23244.

Relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, was more effective than injectable leuprolide at maintaining castration levels of testosterone in men with advanced prostate cancer, according to investigators from the phase 3 HERO trial.

Relugolix was also associated with a significantly lower incidence of major adverse cardiovascular events (MACE), reported Neal D. Shore, MD, of the Carolina Urologic Research Center in Myrtle Beach, S.C., in a presentation made as a part of the American Society of Clinical Oncology virtual scientific program. The study was published simultaneously in The New England Journal of Medicine.

“Relugolix is a novel oral GnRH antagonist that has the potential to become a new standard for ADT [androgen-deprivation therapy] in advanced prostate cancer,” Dr. Shore said. He added that a potential advantage of relugolix compared with the leutenizing hormone-releasing hormone (LHRH) agonist leuprolide is the oral agent’s adverse event profile.

“Of note, and importantly, cardiovascular mortality is the leading cause of death for patients with prostate cancer. The percentage of patients with prostate cancer dying of cardiovascular disease has surpassed the percentage of patients dying from prostate cancer itself since the early 1990s. Approximately 30% of men with prostate cancer have known cardiovascular disease, and many more of these patients have comorbid risk factors, including obesity, diabetes, hypertension, and hyperlipidemia,” Dr. Shore said.

LHRH agonists also cause an initial testosterone surge that may cause an early but transient symptom flare. In contrast, relugolix has a direct inhibitory effect on pituitary GnRH receptors, leading to suppression of both leutenizing hormone and follicle-stimulating hormone, with no testosterone flare.
 

Study details

In the HERO trial, men with advanced prostate cancer were randomized in a 2:1 ratio to receive either relugolix at a 360-mg loading dose on day 1 followed by a 120-mg oral dose once daily (n = 622) or leuprolide delivered via depot injection every 3 months (n = 308) for a total of 48 weeks.

About half of all patients in each arm had biochemical (prostate-specific antigen, or “PSA”) relapse, 23% had newly diagnosed androgen-sensitive metastatic disease, and the remaining men (26%-28%) had advanced localized disease.

Patients with a history of a MACE event – a composite of nonfatal myocardial infarction, nonfatal stroke, and death from any cause – within 6 months were excluded.

The median PSA level at baseline was 11.7 mg/mL in the relugolix arm and 9.4 ng/mL in the leuprolide arm. Respective median testosterone levels were 415.8 ng/dL and 395.9 ng/dL.

“Of note, more than 90% of men enrolled in this study had at least one cardiovascular risk factor,” Dr. Shore said. “Tobacco use and obesity were common, as were diabetes and hypertension. Fourteen percent of men reported a prior history of major adverse cardiovascular event, such as a heart attack or stroke; this is lower than the 30% expected in a typical population of men with advanced prostate cancer given the study’s cardiovascular exclusion criteria.”
 

Efficacy

Sustained testosterone suppression to castration levels (less than 50 ng/dL) was achieved through 48 weeks in 96.7% of patients on relugolix, compared with 88.8% of men on leuprolide.

The absolute difference of 7.9% reached the statistical definitions for both noninferiority and superiority of relugolix over leuprolide (P for superiority < .001).

Mean testosterone levels on day 4 had decreased to below 50 ng/dL for relugolix and were maintained at castration levels until the end of treatment. In the leuprolide group, the mean testosterone level on day 4 was 625 ng/dL, which declined to castration levels by day 29 and remained below 50 ng/dL after the end of treatment at week 53. In contrast, testosterone levels in the relugolix arm began to recover immediately after the cessation of therapy.

Results with relugolix were significantly better than with leuprolide for the following endpoints (P < .0001 for all comparisons):

• Proportion of patients with PSA response at day 15 and confirmed at day 29 (79.4% vs. 19.8%)
• Cumulative probability of testosterone suppression to less than 50 ng/dL on day 15 (98.7% vs. 12.05%)
• Cumulative probability of profound testosterone suppression to less than 20 ng/dL on day 15 (78.38% vs. 0.98%)
• Mean follicle-stimulating hormone level at the end of week 24 (1.72 vs. 5.95 IU/L).

Safety

Treatment-related adverse events occurred in 73.6% of patients treated with relugolix and 68.8% of those who received leuprolide. Grade 3 or greater adverse events occurred in 3.4% and 2.6%, respectively. The respective incidences of fatal adverse events were 1.1% and 2.9%.

At 48 weeks, MACE had occurred in 2.9% of patients on relugolix and 6.2% on leuprolide. Among men with a history of a MACE event more than 6 months before study entry, leuprolide was associated with a nearly sixfold increased risk for a new MACE.

The investigators also found that compliance with the assigned medication was greater than 99% in each study arm, allaying concerns that men assigned to the oral therapy might be less likely to faithfully take their medicine.
 

Antagonists vs. agonists

Agents such as relugolix, which are, in effect, LHRH antagonists, have several advantages over LHRH agonists, according to invited discussant Elahe Mostaghel, MD, PhD, of the VA Puget Sound Health Care System and Fred Hutchinson Cancer Research Center, both in Seattle.

“Cost and access aside, antagonists have potential benefits over agonists, each of which may be more or less important, depending on context,” she said.

Antagonists have a more rapid onset of castration, lack the flare response seen with agonists such as leuprolide, and are associated with a significant decrease in risk for MACE.

“Differences in depth and consistency of androgen suppression may also be important. LHRH antagonists may be superior to LHRH agonists in this regard, although this remains to be fully proven, while rapid testosterone recovery and oral administration may also have benefits in particular contexts,” Dr. Mostaghel said.

“It is likely that the anticancer effects of a GnRH antagonist will not be inferior to those of a GnRH agonist and may be beneficial in terms of cardiovascular events that may be life-limiting,” Celestia S. Higano, MD, of the University of Washington in Seattle wrote in an editorial accompanying the HERO study in The New England Journal of Medicine.

“Close monitoring will be required because exposure to oral relugolix for longer than 48 weeks has not been studied and many oral agents are associated with adherence problems, especially if they cause adverse effects,” Dr. Higano added.

The HERO study was supported by Myovant. Dr. Shore disclosed relationships with Myovant and other companies. Dr. Mostaghel disclosed affiliations with Context Therapeutics. Dr. Hinago disclosed grants and fees from various companies, not including Myovant.

SOURCES: Shore ND et al. ASCO 2020, Abstract 5602; N Engl J Med. 2020 May 29. doi: 10.1056/NEJMoa2004325.

Relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, was more effective than injectable leuprolide at maintaining castration levels of testosterone in men with advanced prostate cancer, according to investigators from the phase 3 HERO trial.

Relugolix was also associated with a significantly lower incidence of major adverse cardiovascular events (MACE), reported Neal D. Shore, MD, of the Carolina Urologic Research Center in Myrtle Beach, S.C., in a presentation made as a part of the American Society of Clinical Oncology virtual scientific program. The study was published simultaneously in The New England Journal of Medicine.

“Relugolix is a novel oral GnRH antagonist that has the potential to become a new standard for ADT [androgen-deprivation therapy] in advanced prostate cancer,” Dr. Shore said. He added that a potential advantage of relugolix compared with the leutenizing hormone-releasing hormone (LHRH) agonist leuprolide is the oral agent’s adverse event profile.

“Of note, and importantly, cardiovascular mortality is the leading cause of death for patients with prostate cancer. The percentage of patients with prostate cancer dying of cardiovascular disease has surpassed the percentage of patients dying from prostate cancer itself since the early 1990s. Approximately 30% of men with prostate cancer have known cardiovascular disease, and many more of these patients have comorbid risk factors, including obesity, diabetes, hypertension, and hyperlipidemia,” Dr. Shore said.

LHRH agonists also cause an initial testosterone surge that may cause an early but transient symptom flare. In contrast, relugolix has a direct inhibitory effect on pituitary GnRH receptors, leading to suppression of both leutenizing hormone and follicle-stimulating hormone, with no testosterone flare.
 

Study details

In the HERO trial, men with advanced prostate cancer were randomized in a 2:1 ratio to receive either relugolix at a 360-mg loading dose on day 1 followed by a 120-mg oral dose once daily (n = 622) or leuprolide delivered via depot injection every 3 months (n = 308) for a total of 48 weeks.

About half of all patients in each arm had biochemical (prostate-specific antigen, or “PSA”) relapse, 23% had newly diagnosed androgen-sensitive metastatic disease, and the remaining men (26%-28%) had advanced localized disease.

Patients with a history of a MACE event – a composite of nonfatal myocardial infarction, nonfatal stroke, and death from any cause – within 6 months were excluded.

The median PSA level at baseline was 11.7 mg/mL in the relugolix arm and 9.4 ng/mL in the leuprolide arm. Respective median testosterone levels were 415.8 ng/dL and 395.9 ng/dL.

“Of note, more than 90% of men enrolled in this study had at least one cardiovascular risk factor,” Dr. Shore said. “Tobacco use and obesity were common, as were diabetes and hypertension. Fourteen percent of men reported a prior history of major adverse cardiovascular event, such as a heart attack or stroke; this is lower than the 30% expected in a typical population of men with advanced prostate cancer given the study’s cardiovascular exclusion criteria.”
 

Efficacy

Sustained testosterone suppression to castration levels (less than 50 ng/dL) was achieved through 48 weeks in 96.7% of patients on relugolix, compared with 88.8% of men on leuprolide.

The absolute difference of 7.9% reached the statistical definitions for both noninferiority and superiority of relugolix over leuprolide (P for superiority < .001).

Mean testosterone levels on day 4 had decreased to below 50 ng/dL for relugolix and were maintained at castration levels until the end of treatment. In the leuprolide group, the mean testosterone level on day 4 was 625 ng/dL, which declined to castration levels by day 29 and remained below 50 ng/dL after the end of treatment at week 53. In contrast, testosterone levels in the relugolix arm began to recover immediately after the cessation of therapy.

Results with relugolix were significantly better than with leuprolide for the following endpoints (P < .0001 for all comparisons):

• Proportion of patients with PSA response at day 15 and confirmed at day 29 (79.4% vs. 19.8%)
• Cumulative probability of testosterone suppression to less than 50 ng/dL on day 15 (98.7% vs. 12.05%)
• Cumulative probability of profound testosterone suppression to less than 20 ng/dL on day 15 (78.38% vs. 0.98%)
• Mean follicle-stimulating hormone level at the end of week 24 (1.72 vs. 5.95 IU/L).

Safety

Treatment-related adverse events occurred in 73.6% of patients treated with relugolix and 68.8% of those who received leuprolide. Grade 3 or greater adverse events occurred in 3.4% and 2.6%, respectively. The respective incidences of fatal adverse events were 1.1% and 2.9%.

At 48 weeks, MACE had occurred in 2.9% of patients on relugolix and 6.2% on leuprolide. Among men with a history of a MACE event more than 6 months before study entry, leuprolide was associated with a nearly sixfold increased risk for a new MACE.

The investigators also found that compliance with the assigned medication was greater than 99% in each study arm, allaying concerns that men assigned to the oral therapy might be less likely to faithfully take their medicine.
 

Antagonists vs. agonists

Agents such as relugolix, which are, in effect, LHRH antagonists, have several advantages over LHRH agonists, according to invited discussant Elahe Mostaghel, MD, PhD, of the VA Puget Sound Health Care System and Fred Hutchinson Cancer Research Center, both in Seattle.

“Cost and access aside, antagonists have potential benefits over agonists, each of which may be more or less important, depending on context,” she said.

Antagonists have a more rapid onset of castration, lack the flare response seen with agonists such as leuprolide, and are associated with a significant decrease in risk for MACE.

“Differences in depth and consistency of androgen suppression may also be important. LHRH antagonists may be superior to LHRH agonists in this regard, although this remains to be fully proven, while rapid testosterone recovery and oral administration may also have benefits in particular contexts,” Dr. Mostaghel said.

“It is likely that the anticancer effects of a GnRH antagonist will not be inferior to those of a GnRH agonist and may be beneficial in terms of cardiovascular events that may be life-limiting,” Celestia S. Higano, MD, of the University of Washington in Seattle wrote in an editorial accompanying the HERO study in The New England Journal of Medicine.

“Close monitoring will be required because exposure to oral relugolix for longer than 48 weeks has not been studied and many oral agents are associated with adherence problems, especially if they cause adverse effects,” Dr. Higano added.

The HERO study was supported by Myovant. Dr. Shore disclosed relationships with Myovant and other companies. Dr. Mostaghel disclosed affiliations with Context Therapeutics. Dr. Hinago disclosed grants and fees from various companies, not including Myovant.

SOURCES: Shore ND et al. ASCO 2020, Abstract 5602; N Engl J Med. 2020 May 29. doi: 10.1056/NEJMoa2004325.

Relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, was more effective than injectable leuprolide at maintaining castration levels of testosterone in men with advanced prostate cancer, according to investigators from the phase 3 HERO trial.

Relugolix was also associated with a significantly lower incidence of major adverse cardiovascular events (MACE), reported Neal D. Shore, MD, of the Carolina Urologic Research Center in Myrtle Beach, S.C., in a presentation made as a part of the American Society of Clinical Oncology virtual scientific program. The study was published simultaneously in The New England Journal of Medicine.

“Relugolix is a novel oral GnRH antagonist that has the potential to become a new standard for ADT [androgen-deprivation therapy] in advanced prostate cancer,” Dr. Shore said. He added that a potential advantage of relugolix compared with the leutenizing hormone-releasing hormone (LHRH) agonist leuprolide is the oral agent’s adverse event profile.

“Of note, and importantly, cardiovascular mortality is the leading cause of death for patients with prostate cancer. The percentage of patients with prostate cancer dying of cardiovascular disease has surpassed the percentage of patients dying from prostate cancer itself since the early 1990s. Approximately 30% of men with prostate cancer have known cardiovascular disease, and many more of these patients have comorbid risk factors, including obesity, diabetes, hypertension, and hyperlipidemia,” Dr. Shore said.

LHRH agonists also cause an initial testosterone surge that may cause an early but transient symptom flare. In contrast, relugolix has a direct inhibitory effect on pituitary GnRH receptors, leading to suppression of both leutenizing hormone and follicle-stimulating hormone, with no testosterone flare.
 

Study details

In the HERO trial, men with advanced prostate cancer were randomized in a 2:1 ratio to receive either relugolix at a 360-mg loading dose on day 1 followed by a 120-mg oral dose once daily (n = 622) or leuprolide delivered via depot injection every 3 months (n = 308) for a total of 48 weeks.

About half of all patients in each arm had biochemical (prostate-specific antigen, or “PSA”) relapse, 23% had newly diagnosed androgen-sensitive metastatic disease, and the remaining men (26%-28%) had advanced localized disease.

Patients with a history of a MACE event – a composite of nonfatal myocardial infarction, nonfatal stroke, and death from any cause – within 6 months were excluded.

The median PSA level at baseline was 11.7 mg/mL in the relugolix arm and 9.4 ng/mL in the leuprolide arm. Respective median testosterone levels were 415.8 ng/dL and 395.9 ng/dL.

“Of note, more than 90% of men enrolled in this study had at least one cardiovascular risk factor,” Dr. Shore said. “Tobacco use and obesity were common, as were diabetes and hypertension. Fourteen percent of men reported a prior history of major adverse cardiovascular event, such as a heart attack or stroke; this is lower than the 30% expected in a typical population of men with advanced prostate cancer given the study’s cardiovascular exclusion criteria.”
 

Efficacy

Sustained testosterone suppression to castration levels (less than 50 ng/dL) was achieved through 48 weeks in 96.7% of patients on relugolix, compared with 88.8% of men on leuprolide.

The absolute difference of 7.9% reached the statistical definitions for both noninferiority and superiority of relugolix over leuprolide (P for superiority < .001).

Mean testosterone levels on day 4 had decreased to below 50 ng/dL for relugolix and were maintained at castration levels until the end of treatment. In the leuprolide group, the mean testosterone level on day 4 was 625 ng/dL, which declined to castration levels by day 29 and remained below 50 ng/dL after the end of treatment at week 53. In contrast, testosterone levels in the relugolix arm began to recover immediately after the cessation of therapy.

Results with relugolix were significantly better than with leuprolide for the following endpoints (P < .0001 for all comparisons):

• Proportion of patients with PSA response at day 15 and confirmed at day 29 (79.4% vs. 19.8%)
• Cumulative probability of testosterone suppression to less than 50 ng/dL on day 15 (98.7% vs. 12.05%)
• Cumulative probability of profound testosterone suppression to less than 20 ng/dL on day 15 (78.38% vs. 0.98%)
• Mean follicle-stimulating hormone level at the end of week 24 (1.72 vs. 5.95 IU/L).

Safety

Treatment-related adverse events occurred in 73.6% of patients treated with relugolix and 68.8% of those who received leuprolide. Grade 3 or greater adverse events occurred in 3.4% and 2.6%, respectively. The respective incidences of fatal adverse events were 1.1% and 2.9%.

At 48 weeks, MACE had occurred in 2.9% of patients on relugolix and 6.2% on leuprolide. Among men with a history of a MACE event more than 6 months before study entry, leuprolide was associated with a nearly sixfold increased risk for a new MACE.

The investigators also found that compliance with the assigned medication was greater than 99% in each study arm, allaying concerns that men assigned to the oral therapy might be less likely to faithfully take their medicine.
 

Antagonists vs. agonists

Agents such as relugolix, which are, in effect, LHRH antagonists, have several advantages over LHRH agonists, according to invited discussant Elahe Mostaghel, MD, PhD, of the VA Puget Sound Health Care System and Fred Hutchinson Cancer Research Center, both in Seattle.

“Cost and access aside, antagonists have potential benefits over agonists, each of which may be more or less important, depending on context,” she said.

Antagonists have a more rapid onset of castration, lack the flare response seen with agonists such as leuprolide, and are associated with a significant decrease in risk for MACE.

“Differences in depth and consistency of androgen suppression may also be important. LHRH antagonists may be superior to LHRH agonists in this regard, although this remains to be fully proven, while rapid testosterone recovery and oral administration may also have benefits in particular contexts,” Dr. Mostaghel said.

“It is likely that the anticancer effects of a GnRH antagonist will not be inferior to those of a GnRH agonist and may be beneficial in terms of cardiovascular events that may be life-limiting,” Celestia S. Higano, MD, of the University of Washington in Seattle wrote in an editorial accompanying the HERO study in The New England Journal of Medicine.

“Close monitoring will be required because exposure to oral relugolix for longer than 48 weeks has not been studied and many oral agents are associated with adherence problems, especially if they cause adverse effects,” Dr. Higano added.

The HERO study was supported by Myovant. Dr. Shore disclosed relationships with Myovant and other companies. Dr. Mostaghel disclosed affiliations with Context Therapeutics. Dr. Hinago disclosed grants and fees from various companies, not including Myovant.

SOURCES: Shore ND et al. ASCO 2020, Abstract 5602; N Engl J Med. 2020 May 29. doi: 10.1056/NEJMoa2004325.