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Leaders Outline DHA “Market” Transition
One theme emerged from multiple military healthy system (MHS) leaders at the recent AMSUS annual conference: Significant change is coming to the MHS, and military health care providers can either embrace and shape that change or somebody else will. “If we don’t shape our future, others will step in and do it for us,” Tom McCaffrey, Assistant Secretary of Defense for Health Affairs; Defense Health Agency (DHA), and the Uniformed Service University for the Health Sciences (USU) told the audience.
The “historic” changes are underway, as the DHA has already begun to take over control of many military treatment facilities (MTFs) that were formerly operated by the separate services. In the next step of the transition, nearly 250 individual MTFs will be combined—along with TRICARE providers—in 21 geographically based “markets” in order to streamline management and avoid redundancies.
The exact details of the changes in store have not been released. McCaffrey noted that US Department of Defense (DoD) leadership will submit the “framework” for their assessment of the MHS to Congress “very soon, and at that point we will begin the hard work of detailed implementation of the results of that assessment and recommendations from the department.” Changes are expected to continue through fiscal year 2021, and some sources have estimated that as many as 18,000 jobs could be eliminated in the process.
Although Congress drove these changes in the National Defense Authorization Act of 2017, MHS leaders insist they are determining how to make the transformation without hurting medical readiness. “We the senior leadership of the MHS must continue to work together to shape our system to meet the challenges of the new environment,” McCaffrey insisted.
It seems as though all elements of the MHS are on the table. One report has suggested that the USU budget could be cut by a third. “Given the USU’s track record of excellence, we were alarmed to learn that the department is considering cuts as high as 30% to the university’s budget for research, development, testing, and evaluation, and 34% to university operations and maintenance... includ[ing] the cancellation of a $445 million military construction project and closure of the USU medical school,” US senators Chris Van Hollen (D-MD), Ben Cardin (D-MD.), Jack Reed (D-RI), and Congressman Jamie Raskin (D-MD) wrote in a November 21, 2019, letter to US Department of Defense Secretary Mark Esper. “These cuts, even if only partially implemented or scaled back, will adversely impact the enterprise across recruitment, retention, access to research funding, and severely impact medical readiness at a time when demand is increasing.”
The medical readiness of military health care providers remains one of the thorniest challenges revolving around the DHA transition. “As an infantryman, from my perspective if you can't maintain effectiveness on the trauma side than it is not worth getting more efficient,” argued LTG (Ret) Jeffrey S. Buchannon, who formerly served as senior commander of Fort Sam Houston, which includes Brooke Army Medical Center, the military’s only level 1 trauma center and 1 of only 2 trauma centers in San Antonio. “We need the home game in order to prepare for the away game,”
In its review, DoD is looking at how the MTFs support inpatient and/or outpatient services to maintain medical force readiness. “We need to identify those areas where we can expand capacity at MTFs that offer potential for sustaining the skills and knowledge of our members,” said McCaffrey. “But we also must examine those areas where facilities do not offer now and likely will not be able to offer in the future a platform for maximizing capabilities to support medical readiness. In those situations, we must be open to right sizing MTF services and capabilities so as to ensure that we are using finite resources most efficiently while not compromising our ability to meet the mission.”
“Our military healthy system is the envy of the world. Any great power competitor would trade its health care and battlefield medicine capabilities for the system you have built,” McCaffrey said. “But just as America’s combat supremacy is not guaranteed nor is the supremacy of the MHS.” The US faces new global security challenges, McCaffrey argued, and “we must adapt and evolve if we are to successfully meet these challenges.”
One theme emerged from multiple military healthy system (MHS) leaders at the recent AMSUS annual conference: Significant change is coming to the MHS, and military health care providers can either embrace and shape that change or somebody else will. “If we don’t shape our future, others will step in and do it for us,” Tom McCaffrey, Assistant Secretary of Defense for Health Affairs; Defense Health Agency (DHA), and the Uniformed Service University for the Health Sciences (USU) told the audience.
The “historic” changes are underway, as the DHA has already begun to take over control of many military treatment facilities (MTFs) that were formerly operated by the separate services. In the next step of the transition, nearly 250 individual MTFs will be combined—along with TRICARE providers—in 21 geographically based “markets” in order to streamline management and avoid redundancies.
The exact details of the changes in store have not been released. McCaffrey noted that US Department of Defense (DoD) leadership will submit the “framework” for their assessment of the MHS to Congress “very soon, and at that point we will begin the hard work of detailed implementation of the results of that assessment and recommendations from the department.” Changes are expected to continue through fiscal year 2021, and some sources have estimated that as many as 18,000 jobs could be eliminated in the process.
Although Congress drove these changes in the National Defense Authorization Act of 2017, MHS leaders insist they are determining how to make the transformation without hurting medical readiness. “We the senior leadership of the MHS must continue to work together to shape our system to meet the challenges of the new environment,” McCaffrey insisted.
It seems as though all elements of the MHS are on the table. One report has suggested that the USU budget could be cut by a third. “Given the USU’s track record of excellence, we were alarmed to learn that the department is considering cuts as high as 30% to the university’s budget for research, development, testing, and evaluation, and 34% to university operations and maintenance... includ[ing] the cancellation of a $445 million military construction project and closure of the USU medical school,” US senators Chris Van Hollen (D-MD), Ben Cardin (D-MD.), Jack Reed (D-RI), and Congressman Jamie Raskin (D-MD) wrote in a November 21, 2019, letter to US Department of Defense Secretary Mark Esper. “These cuts, even if only partially implemented or scaled back, will adversely impact the enterprise across recruitment, retention, access to research funding, and severely impact medical readiness at a time when demand is increasing.”
The medical readiness of military health care providers remains one of the thorniest challenges revolving around the DHA transition. “As an infantryman, from my perspective if you can't maintain effectiveness on the trauma side than it is not worth getting more efficient,” argued LTG (Ret) Jeffrey S. Buchannon, who formerly served as senior commander of Fort Sam Houston, which includes Brooke Army Medical Center, the military’s only level 1 trauma center and 1 of only 2 trauma centers in San Antonio. “We need the home game in order to prepare for the away game,”
In its review, DoD is looking at how the MTFs support inpatient and/or outpatient services to maintain medical force readiness. “We need to identify those areas where we can expand capacity at MTFs that offer potential for sustaining the skills and knowledge of our members,” said McCaffrey. “But we also must examine those areas where facilities do not offer now and likely will not be able to offer in the future a platform for maximizing capabilities to support medical readiness. In those situations, we must be open to right sizing MTF services and capabilities so as to ensure that we are using finite resources most efficiently while not compromising our ability to meet the mission.”
“Our military healthy system is the envy of the world. Any great power competitor would trade its health care and battlefield medicine capabilities for the system you have built,” McCaffrey said. “But just as America’s combat supremacy is not guaranteed nor is the supremacy of the MHS.” The US faces new global security challenges, McCaffrey argued, and “we must adapt and evolve if we are to successfully meet these challenges.”
One theme emerged from multiple military healthy system (MHS) leaders at the recent AMSUS annual conference: Significant change is coming to the MHS, and military health care providers can either embrace and shape that change or somebody else will. “If we don’t shape our future, others will step in and do it for us,” Tom McCaffrey, Assistant Secretary of Defense for Health Affairs; Defense Health Agency (DHA), and the Uniformed Service University for the Health Sciences (USU) told the audience.
The “historic” changes are underway, as the DHA has already begun to take over control of many military treatment facilities (MTFs) that were formerly operated by the separate services. In the next step of the transition, nearly 250 individual MTFs will be combined—along with TRICARE providers—in 21 geographically based “markets” in order to streamline management and avoid redundancies.
The exact details of the changes in store have not been released. McCaffrey noted that US Department of Defense (DoD) leadership will submit the “framework” for their assessment of the MHS to Congress “very soon, and at that point we will begin the hard work of detailed implementation of the results of that assessment and recommendations from the department.” Changes are expected to continue through fiscal year 2021, and some sources have estimated that as many as 18,000 jobs could be eliminated in the process.
Although Congress drove these changes in the National Defense Authorization Act of 2017, MHS leaders insist they are determining how to make the transformation without hurting medical readiness. “We the senior leadership of the MHS must continue to work together to shape our system to meet the challenges of the new environment,” McCaffrey insisted.
It seems as though all elements of the MHS are on the table. One report has suggested that the USU budget could be cut by a third. “Given the USU’s track record of excellence, we were alarmed to learn that the department is considering cuts as high as 30% to the university’s budget for research, development, testing, and evaluation, and 34% to university operations and maintenance... includ[ing] the cancellation of a $445 million military construction project and closure of the USU medical school,” US senators Chris Van Hollen (D-MD), Ben Cardin (D-MD.), Jack Reed (D-RI), and Congressman Jamie Raskin (D-MD) wrote in a November 21, 2019, letter to US Department of Defense Secretary Mark Esper. “These cuts, even if only partially implemented or scaled back, will adversely impact the enterprise across recruitment, retention, access to research funding, and severely impact medical readiness at a time when demand is increasing.”
The medical readiness of military health care providers remains one of the thorniest challenges revolving around the DHA transition. “As an infantryman, from my perspective if you can't maintain effectiveness on the trauma side than it is not worth getting more efficient,” argued LTG (Ret) Jeffrey S. Buchannon, who formerly served as senior commander of Fort Sam Houston, which includes Brooke Army Medical Center, the military’s only level 1 trauma center and 1 of only 2 trauma centers in San Antonio. “We need the home game in order to prepare for the away game,”
In its review, DoD is looking at how the MTFs support inpatient and/or outpatient services to maintain medical force readiness. “We need to identify those areas where we can expand capacity at MTFs that offer potential for sustaining the skills and knowledge of our members,” said McCaffrey. “But we also must examine those areas where facilities do not offer now and likely will not be able to offer in the future a platform for maximizing capabilities to support medical readiness. In those situations, we must be open to right sizing MTF services and capabilities so as to ensure that we are using finite resources most efficiently while not compromising our ability to meet the mission.”
“Our military healthy system is the envy of the world. Any great power competitor would trade its health care and battlefield medicine capabilities for the system you have built,” McCaffrey said. “But just as America’s combat supremacy is not guaranteed nor is the supremacy of the MHS.” The US faces new global security challenges, McCaffrey argued, and “we must adapt and evolve if we are to successfully meet these challenges.”
Orelabrutinib could be ‘preferred’ BTK inhibitor for MCL
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
REPORTING FROM ASH 2019
Tucatinib called game-changer in HER2-positive metastatic breast cancer
SAN ANTONIO – Tucatinib, an investigational oral inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase, constitutes a major advance in the treatment of heavily pretreated HER2-positive metastatic breast cancer – including patients with brain metastases, Rashmi K. Murthy, MD, declared at the San Antonio Breast Cancer Symposium.
She presented the results of the pivotal HER2CLIMB trial, in which 612 women with heavily pretreated HER2-positive metastatic breast cancer were randomized two-to-one to oral tucatinib at 300 mg twice daily or placebo in combination with standard guideline-recommended treatment with trastuzumab and capecitabine. This landmark double-blind study, conducted at 155 sites in 15 countries, was the first-ever randomized trial to include HER2-positive metastatic breast cancer patients with baseline untreated or previously treated but progressing brain metastases; indeed, nearly half of participants had baseline brain metastases, 40% of which were untreated or treated and progressing.
Not only did tucatinib on top of background trastuzumab and capecitabine reduce the risk of death by 34% compared with placebo, it also more than doubled progression-free survival. And most encouragingly, it did so in patients with or without baseline brain metastases.
“I would like to take a minute here to highlight that this overall survival benefit was seen in patients who had already received trastuzumab, pertuzumab, and T-DM1 [trastuzumab emtansine] and included patients who had brain metastases. Tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in this population with and without brain metastases,” said Dr. Murthy, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
Tucatinib, which crosses the blood-brain barrier, is highly selective for the kinase domain of HER2, with only miniscule inhibition of epidermal growth factor receptor. Its high selectivity is reflected in a favorable tolerability profile: Only 6% of patients discontinued tucatinib because of adverse events. This low discontinuation rate permitted longer treatment, even in this heavily pretreated population.
The most common adverse events in the tucatinib study arm were diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting, with most cases being low grade. Diarrhea, the most common adverse event, occurred in 81% of tucatinib-treated patients and 53% of controls. However, only 13% of the tucatinib group experienced grade 3 or worse diarrhea. Notably, antidiarrheal prophylaxis wasn’t mandated in HER2CLIMB. Antidiarrheal medications were utilized in less than half of the treatment cycles where diarrhea was reported, and even then, for a median of only 3 days per cycle.
Median study follow-up was 14 months. The primary study endpoint – 1-year progression-free survival assessed by blinded independent central review – was 33% in the tucatinib group and 12% in controls. Thus, the risk of disease progression or death was reduced by 46% in the tucatinib group. The median duration of progression-free survival was 7.8 months in tucatinib-treated patients, compared with 5.6 months in controls.
Two-year estimated overall survival was 45% with tucatinib and 27% with placebo. The tucatinib group’s 21.9-month median overall survival was 4.5 months greater than in controls.
One-year estimated progression-free survival in patients with baseline brain metastases was 25% in the tucatinib group and zero in controls.
The confirmed objective response rate was 41% in the tucatinib group, nearly double the 23% figure in controls.
The overall and progression-free survival results were consistent across all prespecified subgroups based upon age, race, hormone receptor status, geographic location, and other factors.
The study met with an extremely favorable reception peppered with comments such as “tremendous results.”
“I think that the HER2CLIMB study is practice-changing,” Hope S. Rugo, MD, said in an interview.
“The overall survival benefit in all patients and in those who have brain metastases is clinically relevant for our patients who have HER2-positive metastatic breast cancer treated with trastuzumab, pertuzumab, and T-DMI. In addition, the toxicity profile is superior to prior oral TKIs, which is a huge issue for our patients with metastatic disease,” observed Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco.
The HER2CLIMB results raise an important question for future research: Namely, could tucatinib have a role in preventing brain metastases by giving the drug earlier in the course of treatment of patients who are at high risk for developing brain metastases, she added.
Simultaneously with Dr. Murthy’s presentation in San Antonio, the HER2CLIMB results were published online in the New England Journal of Medicine.
Dr. Murthy reported receiving institutional research support from and serving as a consultant to Seattle Genetics, sponsor of the HER2CLIMB trial, as well as from several other pharmaceutical companies.
SOURCE: Murthy RK. SABCS 2019 Abstract GS1-01.
SAN ANTONIO – Tucatinib, an investigational oral inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase, constitutes a major advance in the treatment of heavily pretreated HER2-positive metastatic breast cancer – including patients with brain metastases, Rashmi K. Murthy, MD, declared at the San Antonio Breast Cancer Symposium.
She presented the results of the pivotal HER2CLIMB trial, in which 612 women with heavily pretreated HER2-positive metastatic breast cancer were randomized two-to-one to oral tucatinib at 300 mg twice daily or placebo in combination with standard guideline-recommended treatment with trastuzumab and capecitabine. This landmark double-blind study, conducted at 155 sites in 15 countries, was the first-ever randomized trial to include HER2-positive metastatic breast cancer patients with baseline untreated or previously treated but progressing brain metastases; indeed, nearly half of participants had baseline brain metastases, 40% of which were untreated or treated and progressing.
Not only did tucatinib on top of background trastuzumab and capecitabine reduce the risk of death by 34% compared with placebo, it also more than doubled progression-free survival. And most encouragingly, it did so in patients with or without baseline brain metastases.
“I would like to take a minute here to highlight that this overall survival benefit was seen in patients who had already received trastuzumab, pertuzumab, and T-DM1 [trastuzumab emtansine] and included patients who had brain metastases. Tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in this population with and without brain metastases,” said Dr. Murthy, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
Tucatinib, which crosses the blood-brain barrier, is highly selective for the kinase domain of HER2, with only miniscule inhibition of epidermal growth factor receptor. Its high selectivity is reflected in a favorable tolerability profile: Only 6% of patients discontinued tucatinib because of adverse events. This low discontinuation rate permitted longer treatment, even in this heavily pretreated population.
The most common adverse events in the tucatinib study arm were diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting, with most cases being low grade. Diarrhea, the most common adverse event, occurred in 81% of tucatinib-treated patients and 53% of controls. However, only 13% of the tucatinib group experienced grade 3 or worse diarrhea. Notably, antidiarrheal prophylaxis wasn’t mandated in HER2CLIMB. Antidiarrheal medications were utilized in less than half of the treatment cycles where diarrhea was reported, and even then, for a median of only 3 days per cycle.
Median study follow-up was 14 months. The primary study endpoint – 1-year progression-free survival assessed by blinded independent central review – was 33% in the tucatinib group and 12% in controls. Thus, the risk of disease progression or death was reduced by 46% in the tucatinib group. The median duration of progression-free survival was 7.8 months in tucatinib-treated patients, compared with 5.6 months in controls.
Two-year estimated overall survival was 45% with tucatinib and 27% with placebo. The tucatinib group’s 21.9-month median overall survival was 4.5 months greater than in controls.
One-year estimated progression-free survival in patients with baseline brain metastases was 25% in the tucatinib group and zero in controls.
The confirmed objective response rate was 41% in the tucatinib group, nearly double the 23% figure in controls.
The overall and progression-free survival results were consistent across all prespecified subgroups based upon age, race, hormone receptor status, geographic location, and other factors.
The study met with an extremely favorable reception peppered with comments such as “tremendous results.”
“I think that the HER2CLIMB study is practice-changing,” Hope S. Rugo, MD, said in an interview.
“The overall survival benefit in all patients and in those who have brain metastases is clinically relevant for our patients who have HER2-positive metastatic breast cancer treated with trastuzumab, pertuzumab, and T-DMI. In addition, the toxicity profile is superior to prior oral TKIs, which is a huge issue for our patients with metastatic disease,” observed Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco.
The HER2CLIMB results raise an important question for future research: Namely, could tucatinib have a role in preventing brain metastases by giving the drug earlier in the course of treatment of patients who are at high risk for developing brain metastases, she added.
Simultaneously with Dr. Murthy’s presentation in San Antonio, the HER2CLIMB results were published online in the New England Journal of Medicine.
Dr. Murthy reported receiving institutional research support from and serving as a consultant to Seattle Genetics, sponsor of the HER2CLIMB trial, as well as from several other pharmaceutical companies.
SOURCE: Murthy RK. SABCS 2019 Abstract GS1-01.
SAN ANTONIO – Tucatinib, an investigational oral inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase, constitutes a major advance in the treatment of heavily pretreated HER2-positive metastatic breast cancer – including patients with brain metastases, Rashmi K. Murthy, MD, declared at the San Antonio Breast Cancer Symposium.
She presented the results of the pivotal HER2CLIMB trial, in which 612 women with heavily pretreated HER2-positive metastatic breast cancer were randomized two-to-one to oral tucatinib at 300 mg twice daily or placebo in combination with standard guideline-recommended treatment with trastuzumab and capecitabine. This landmark double-blind study, conducted at 155 sites in 15 countries, was the first-ever randomized trial to include HER2-positive metastatic breast cancer patients with baseline untreated or previously treated but progressing brain metastases; indeed, nearly half of participants had baseline brain metastases, 40% of which were untreated or treated and progressing.
Not only did tucatinib on top of background trastuzumab and capecitabine reduce the risk of death by 34% compared with placebo, it also more than doubled progression-free survival. And most encouragingly, it did so in patients with or without baseline brain metastases.
“I would like to take a minute here to highlight that this overall survival benefit was seen in patients who had already received trastuzumab, pertuzumab, and T-DM1 [trastuzumab emtansine] and included patients who had brain metastases. Tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in this population with and without brain metastases,” said Dr. Murthy, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
Tucatinib, which crosses the blood-brain barrier, is highly selective for the kinase domain of HER2, with only miniscule inhibition of epidermal growth factor receptor. Its high selectivity is reflected in a favorable tolerability profile: Only 6% of patients discontinued tucatinib because of adverse events. This low discontinuation rate permitted longer treatment, even in this heavily pretreated population.
The most common adverse events in the tucatinib study arm were diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting, with most cases being low grade. Diarrhea, the most common adverse event, occurred in 81% of tucatinib-treated patients and 53% of controls. However, only 13% of the tucatinib group experienced grade 3 or worse diarrhea. Notably, antidiarrheal prophylaxis wasn’t mandated in HER2CLIMB. Antidiarrheal medications were utilized in less than half of the treatment cycles where diarrhea was reported, and even then, for a median of only 3 days per cycle.
Median study follow-up was 14 months. The primary study endpoint – 1-year progression-free survival assessed by blinded independent central review – was 33% in the tucatinib group and 12% in controls. Thus, the risk of disease progression or death was reduced by 46% in the tucatinib group. The median duration of progression-free survival was 7.8 months in tucatinib-treated patients, compared with 5.6 months in controls.
Two-year estimated overall survival was 45% with tucatinib and 27% with placebo. The tucatinib group’s 21.9-month median overall survival was 4.5 months greater than in controls.
One-year estimated progression-free survival in patients with baseline brain metastases was 25% in the tucatinib group and zero in controls.
The confirmed objective response rate was 41% in the tucatinib group, nearly double the 23% figure in controls.
The overall and progression-free survival results were consistent across all prespecified subgroups based upon age, race, hormone receptor status, geographic location, and other factors.
The study met with an extremely favorable reception peppered with comments such as “tremendous results.”
“I think that the HER2CLIMB study is practice-changing,” Hope S. Rugo, MD, said in an interview.
“The overall survival benefit in all patients and in those who have brain metastases is clinically relevant for our patients who have HER2-positive metastatic breast cancer treated with trastuzumab, pertuzumab, and T-DMI. In addition, the toxicity profile is superior to prior oral TKIs, which is a huge issue for our patients with metastatic disease,” observed Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco.
The HER2CLIMB results raise an important question for future research: Namely, could tucatinib have a role in preventing brain metastases by giving the drug earlier in the course of treatment of patients who are at high risk for developing brain metastases, she added.
Simultaneously with Dr. Murthy’s presentation in San Antonio, the HER2CLIMB results were published online in the New England Journal of Medicine.
Dr. Murthy reported receiving institutional research support from and serving as a consultant to Seattle Genetics, sponsor of the HER2CLIMB trial, as well as from several other pharmaceutical companies.
SOURCE: Murthy RK. SABCS 2019 Abstract GS1-01.
REPORTING FROM SABCS 2019
Trastuzumab deruxtecan has good activity in advanced HER2-positive breast cancer
SAN ANTONIO –A novel antibody-drug conjugate pairing trastuzumab (Herceptin) with a topoisomerase I inhibitor as the toxic payload was associated with a good overall response rate in patients with heavily pretreated HER2-positive metastatic breast cancer.
The confirmed overall response rate among 184 patients treated with trastuzumab deruxtecan and followed for a median of 11.1 months was 60.9%, consisting of 6% complete responses and 54.9% partial responses, reported Ian Krop, MD, PhD, from the Dana-Farber Cancer Institute in Boston.
“These data demonstrate the potential of trastuzumab deruxtecan to establish a new standard of care for patients with advanced HER2-positive breast cancer,” he said at a briefing prior to presentation of the data at the San Antonio Breast Cancer Symposium.
Results of the open-label phase 2 DESTINY-BREAST01 study were also published online in the New England Journal of Medicine.
Although the antibody-drug conjugate was associated with a good response rate among heavily pretreated patients (median of six prior lines of therapy), it was also associated with interstitial lung disease (ILD), including 4 fatalities among 184 patients who received the drug at the recommended study dose of 5.4 mg/kg.
“ILD is confirmed as an important risk of trastuzumab deruxtecan, it can be severe, and requires careful monitoring and prompt intervention,” Dr. Krop said.
Trastuzumab deruxtecan is composed of a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab, and exatecan derivative as the topoisomerase I inhibitor payload conjugated by a tetrapeptide-based cleavable linker.
Although topoisomerase I inhibitors are not commonly used in breast cancer because of limited activity in clinical trials and toxicities when used systemically, the rationale for using a topoisomerase I inhibitor in this setting is that the toxic effects can be largely confined to the local tumor environment.
In addition, “this is an agent that the cancers generally haven’t been exposed to, so there is the hope this will be non–cross-resistant,” Dr. Krop said at the briefing.
The product has a high drug molecule-to-antibody ratio or approximately 8:1, which is higher than that seen with other antibody-drug conjugates, and the topoisomerase inhibitor payload is membrane permeable, giving it extra potency.
Study details
DESTINY-BREAST01 is an open-label, multicenter, phase 2 study consisting of a dose-finding phase and a continuous phase. Dr. Krop reported on all 184 patients who have been treated at the recommend 5.4-mg/kg dose.
As noted, the patients had received a median of 6 prior lines of therapy, with at least one patient receiving a staggering 27 prior lines. All had previously received trastuzumab and a different antibody-drug conjugate, ado-trastuzumab emtansine (T-DMI; Kadcyla). Two-thirds of patients (65.8%) had received pertuzumab (Perjeta), 54.3% received other anti-HER2 therapies. 48.9% had received hormone therapy, and 99.5% had received other systemic therapies.
ORR by independent review, the primary endpoint, was as noted before. In addition to the 60.9% ORR, 36.4% of patients had stable disease, for a disease control rate of 97.3%.
The median time to response was 1.6 month, and the median duration of response was 14.8 months.
The median progression-free survival at follow-up was 16.4 months. The median overall survival had not been reached at the time of data cutoff in August 2019.
Interstitial lung disease
After a median treatment duration of 10 months, all but one patient had at least one drug-related adverse event. Grade 3 or greater drug-related adverse events occurred in 48.4% of patients, and serious drug-related events occurred in 12.5%.
A total of 25 patients had ILD of any grade, including 5 with grade 1, 15 with grade 2, 1 with grade 4, and the aforementioned 4 patients who died from the disease.
In the four patients with fatal ILD, onset ranged from 63-146, with the deaths occurring 9-60 days after ILD diagnosis. Three of the patients had received steroids as part of their ILD treatment.
The investigators recommend close monitoring of patients for signs and symptoms of lung disease, including fever, cough, or dyspnea. They also recommend that patients with suspected ILD be evaluated with high-resolution CT and testing for pulmonary function and oxygen saturation, ideally under consultation with a pulmonologist.
However, despite the known cardiotoxic effects of trastuzumab, there were no reported cases of heart failure with decline in left ventricular ejection fraction, and only three patients had a decrease in left ventricular ejection fraction, none of which grade 4.
“The response rate and overall efficacy observed with trastuzumab deruxtecan in this study appear to substantially exceed those of currently available HER2-directed regimens and new agents in development, although cross-trial comparisons must be interpreted with caution,” the investigators wrote in the New England Journal of Medicine.
The study was funded by Daiichi Sankyo and AstraZeneca. Dr. Krop disclosed consulting fees, honoraria from each company, and research support from Genentech/Roche and Pfizer.
SOURCE: Krop I et al. SABCS 2019, Abstract GS1-03.
SAN ANTONIO –A novel antibody-drug conjugate pairing trastuzumab (Herceptin) with a topoisomerase I inhibitor as the toxic payload was associated with a good overall response rate in patients with heavily pretreated HER2-positive metastatic breast cancer.
The confirmed overall response rate among 184 patients treated with trastuzumab deruxtecan and followed for a median of 11.1 months was 60.9%, consisting of 6% complete responses and 54.9% partial responses, reported Ian Krop, MD, PhD, from the Dana-Farber Cancer Institute in Boston.
“These data demonstrate the potential of trastuzumab deruxtecan to establish a new standard of care for patients with advanced HER2-positive breast cancer,” he said at a briefing prior to presentation of the data at the San Antonio Breast Cancer Symposium.
Results of the open-label phase 2 DESTINY-BREAST01 study were also published online in the New England Journal of Medicine.
Although the antibody-drug conjugate was associated with a good response rate among heavily pretreated patients (median of six prior lines of therapy), it was also associated with interstitial lung disease (ILD), including 4 fatalities among 184 patients who received the drug at the recommended study dose of 5.4 mg/kg.
“ILD is confirmed as an important risk of trastuzumab deruxtecan, it can be severe, and requires careful monitoring and prompt intervention,” Dr. Krop said.
Trastuzumab deruxtecan is composed of a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab, and exatecan derivative as the topoisomerase I inhibitor payload conjugated by a tetrapeptide-based cleavable linker.
Although topoisomerase I inhibitors are not commonly used in breast cancer because of limited activity in clinical trials and toxicities when used systemically, the rationale for using a topoisomerase I inhibitor in this setting is that the toxic effects can be largely confined to the local tumor environment.
In addition, “this is an agent that the cancers generally haven’t been exposed to, so there is the hope this will be non–cross-resistant,” Dr. Krop said at the briefing.
The product has a high drug molecule-to-antibody ratio or approximately 8:1, which is higher than that seen with other antibody-drug conjugates, and the topoisomerase inhibitor payload is membrane permeable, giving it extra potency.
Study details
DESTINY-BREAST01 is an open-label, multicenter, phase 2 study consisting of a dose-finding phase and a continuous phase. Dr. Krop reported on all 184 patients who have been treated at the recommend 5.4-mg/kg dose.
As noted, the patients had received a median of 6 prior lines of therapy, with at least one patient receiving a staggering 27 prior lines. All had previously received trastuzumab and a different antibody-drug conjugate, ado-trastuzumab emtansine (T-DMI; Kadcyla). Two-thirds of patients (65.8%) had received pertuzumab (Perjeta), 54.3% received other anti-HER2 therapies. 48.9% had received hormone therapy, and 99.5% had received other systemic therapies.
ORR by independent review, the primary endpoint, was as noted before. In addition to the 60.9% ORR, 36.4% of patients had stable disease, for a disease control rate of 97.3%.
The median time to response was 1.6 month, and the median duration of response was 14.8 months.
The median progression-free survival at follow-up was 16.4 months. The median overall survival had not been reached at the time of data cutoff in August 2019.
Interstitial lung disease
After a median treatment duration of 10 months, all but one patient had at least one drug-related adverse event. Grade 3 or greater drug-related adverse events occurred in 48.4% of patients, and serious drug-related events occurred in 12.5%.
A total of 25 patients had ILD of any grade, including 5 with grade 1, 15 with grade 2, 1 with grade 4, and the aforementioned 4 patients who died from the disease.
In the four patients with fatal ILD, onset ranged from 63-146, with the deaths occurring 9-60 days after ILD diagnosis. Three of the patients had received steroids as part of their ILD treatment.
The investigators recommend close monitoring of patients for signs and symptoms of lung disease, including fever, cough, or dyspnea. They also recommend that patients with suspected ILD be evaluated with high-resolution CT and testing for pulmonary function and oxygen saturation, ideally under consultation with a pulmonologist.
However, despite the known cardiotoxic effects of trastuzumab, there were no reported cases of heart failure with decline in left ventricular ejection fraction, and only three patients had a decrease in left ventricular ejection fraction, none of which grade 4.
“The response rate and overall efficacy observed with trastuzumab deruxtecan in this study appear to substantially exceed those of currently available HER2-directed regimens and new agents in development, although cross-trial comparisons must be interpreted with caution,” the investigators wrote in the New England Journal of Medicine.
The study was funded by Daiichi Sankyo and AstraZeneca. Dr. Krop disclosed consulting fees, honoraria from each company, and research support from Genentech/Roche and Pfizer.
SOURCE: Krop I et al. SABCS 2019, Abstract GS1-03.
SAN ANTONIO –A novel antibody-drug conjugate pairing trastuzumab (Herceptin) with a topoisomerase I inhibitor as the toxic payload was associated with a good overall response rate in patients with heavily pretreated HER2-positive metastatic breast cancer.
The confirmed overall response rate among 184 patients treated with trastuzumab deruxtecan and followed for a median of 11.1 months was 60.9%, consisting of 6% complete responses and 54.9% partial responses, reported Ian Krop, MD, PhD, from the Dana-Farber Cancer Institute in Boston.
“These data demonstrate the potential of trastuzumab deruxtecan to establish a new standard of care for patients with advanced HER2-positive breast cancer,” he said at a briefing prior to presentation of the data at the San Antonio Breast Cancer Symposium.
Results of the open-label phase 2 DESTINY-BREAST01 study were also published online in the New England Journal of Medicine.
Although the antibody-drug conjugate was associated with a good response rate among heavily pretreated patients (median of six prior lines of therapy), it was also associated with interstitial lung disease (ILD), including 4 fatalities among 184 patients who received the drug at the recommended study dose of 5.4 mg/kg.
“ILD is confirmed as an important risk of trastuzumab deruxtecan, it can be severe, and requires careful monitoring and prompt intervention,” Dr. Krop said.
Trastuzumab deruxtecan is composed of a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab, and exatecan derivative as the topoisomerase I inhibitor payload conjugated by a tetrapeptide-based cleavable linker.
Although topoisomerase I inhibitors are not commonly used in breast cancer because of limited activity in clinical trials and toxicities when used systemically, the rationale for using a topoisomerase I inhibitor in this setting is that the toxic effects can be largely confined to the local tumor environment.
In addition, “this is an agent that the cancers generally haven’t been exposed to, so there is the hope this will be non–cross-resistant,” Dr. Krop said at the briefing.
The product has a high drug molecule-to-antibody ratio or approximately 8:1, which is higher than that seen with other antibody-drug conjugates, and the topoisomerase inhibitor payload is membrane permeable, giving it extra potency.
Study details
DESTINY-BREAST01 is an open-label, multicenter, phase 2 study consisting of a dose-finding phase and a continuous phase. Dr. Krop reported on all 184 patients who have been treated at the recommend 5.4-mg/kg dose.
As noted, the patients had received a median of 6 prior lines of therapy, with at least one patient receiving a staggering 27 prior lines. All had previously received trastuzumab and a different antibody-drug conjugate, ado-trastuzumab emtansine (T-DMI; Kadcyla). Two-thirds of patients (65.8%) had received pertuzumab (Perjeta), 54.3% received other anti-HER2 therapies. 48.9% had received hormone therapy, and 99.5% had received other systemic therapies.
ORR by independent review, the primary endpoint, was as noted before. In addition to the 60.9% ORR, 36.4% of patients had stable disease, for a disease control rate of 97.3%.
The median time to response was 1.6 month, and the median duration of response was 14.8 months.
The median progression-free survival at follow-up was 16.4 months. The median overall survival had not been reached at the time of data cutoff in August 2019.
Interstitial lung disease
After a median treatment duration of 10 months, all but one patient had at least one drug-related adverse event. Grade 3 or greater drug-related adverse events occurred in 48.4% of patients, and serious drug-related events occurred in 12.5%.
A total of 25 patients had ILD of any grade, including 5 with grade 1, 15 with grade 2, 1 with grade 4, and the aforementioned 4 patients who died from the disease.
In the four patients with fatal ILD, onset ranged from 63-146, with the deaths occurring 9-60 days after ILD diagnosis. Three of the patients had received steroids as part of their ILD treatment.
The investigators recommend close monitoring of patients for signs and symptoms of lung disease, including fever, cough, or dyspnea. They also recommend that patients with suspected ILD be evaluated with high-resolution CT and testing for pulmonary function and oxygen saturation, ideally under consultation with a pulmonologist.
However, despite the known cardiotoxic effects of trastuzumab, there were no reported cases of heart failure with decline in left ventricular ejection fraction, and only three patients had a decrease in left ventricular ejection fraction, none of which grade 4.
“The response rate and overall efficacy observed with trastuzumab deruxtecan in this study appear to substantially exceed those of currently available HER2-directed regimens and new agents in development, although cross-trial comparisons must be interpreted with caution,” the investigators wrote in the New England Journal of Medicine.
The study was funded by Daiichi Sankyo and AstraZeneca. Dr. Krop disclosed consulting fees, honoraria from each company, and research support from Genentech/Roche and Pfizer.
SOURCE: Krop I et al. SABCS 2019, Abstract GS1-03.
REPORTING FROM SABCS 2019
Tales of nasal terror, and dental hoverboarding
A cure for nosiness
Christmas may be just around the corner, but is there ever really a wrong time to huddle around a campfire and swap scary stories? So bundle up, get the fire going, and prepare yourselves for a pair of nasal-based horror stories that will frighten your Jingle Bells off!
Our first tale of nostril terror comes all the way from southern India, where a 13-year-old boy jumped into a water well to cool off. Hey, southern India gets hot, even in November. But like something out of a bad sci-fi movie, his peaceful swim was interrupted when something swam up his nose, causing him extreme pain. After a 30-minute procedure, the doctor pulled out the culprit: A horrific alien parasite! Okay, we’re lying; it was a fish. But we had you going, didn’t we?
Well, maybe that didn’t get you frightened. But we have more rhinal dread to share! A young girl in Las Vegas stuck a pair of plastic doll shoes up her nose, one in each nostril. Her mother removed one shoe, but neither she nor urgent care could reach the second. A trip to the hospital was in order, and once there, the doctors were able to remove the foreign object in seconds.
But as with all things in U.S. medicine, a reckoning would soon come. You feel it now, the dread in this woman’s heart when the hospital bill came.
She takes the envelope, and opens it slowly.
The paper unfolds, rough and heavy in her hands.
Her eyes scan the page, looking for the number, where is it, where is it? It must be here, it must be ...
$3,000.
That’s right, for this simple procedure, performed with a pair of fancy tweezers, the hospital saw fit to charge the hapless mother $3,000! AHHHHHHHHHHHH!
Some say that the mother’s high-deductible insurance policy reduced the cost to $1,700. But we ask you, does that make the story any less spooky? We think not.
Hoverboarding down the root canal
Time spent in the dentist’s chair is among the most anxiety-inducing in anyone’s life. The needles. The grinding. The drilling. The rinsing. The spitting. The throbbing copays.
But you know what might inject a few cc’s of fun into your oral hygiene visits?
Did you guess ... a hoverboard?
If you did, well, you’re probably dentist Steve Martin in “Little Shop of Horrors.” Or perhaps Alaska dentist Seth Lookhart, who authorities say performed a tooth extraction on a sedated patient while Dr. Lookhart also rode a hoverboard. There are also charges of felony Medicaid fraud and reckless endangerment. And allegations of hefty theft from his practice partners. Oh, and a state board apparently suspended Dr. Lookhart’s dental license in 2017.
But hey, pulling teeth while taming a hoverboard? Photos or it didn’t happen, right?
Unfortunately for the well-balanced dentist, there are photos. Actually, there’s an entire video. And when prosecutors showed it to Dr. Lookhart’s unwitting and horrified costar, she was about as happy as the impacted wisdom teeth your teen kid’s still toting around.
Dr. Lookhart denied the felony fraud charges. But he did cop to the hoverboard. Which puts him one up on his cinematic “Wild and Crazy Guy” doppelganger. Even as a neurosurgeon in “The Man With Two Brains,” Mr. Martin never attempted to hoverboard while performing double “cranial screw-top” brain surgeries.
CSI: Quebec
They may live in that eternally polite land on the other side of our northern border, but they know where the bodies are buried. Lots of bodies. Some of them in shallow graves. Some of them in vehicles.
No, we are not talking about Gil Grissom and the gang at CSI. We’re talking about the Secure Site for Research in Thanatology, also known as the “body farm,” which is scheduled to open this spring in Becancour, Quebec.
It’s the first such outdoor forensic facility in Canada and the first in the world – there are also body farms in the United States, Australia, and the Netherlands – to be located in a northern climate.
“We’re particularly interested in understanding what happens when a body is in subzero temperatures, when there’s a lot of snow on the ground, and how that freeze and then the thaw process might actually change the rate of decomposition,” Shari Forbes, the farm’s director, told CTV News recently.
The science team will be out on the farm every day, meticulously checking each body – talk about making a list and checking it twice – for all the important CSI stuff: how long fingerprints and DNA evidence last, the effects of insect feeding and egg-laying, and the ability of dogs to detect scents.
The decomposition process in a cold climate will be a strange and wondrous journey, and the body farm’s work can, perhaps, best be summed up by none other than Mr. Grissom, who once said that getting to the evidence means having to destroy the evidence.
Then again, he also said that “dead men don’t ride roller coasters,” so the analogy only goes so far.
A cure for nosiness
Christmas may be just around the corner, but is there ever really a wrong time to huddle around a campfire and swap scary stories? So bundle up, get the fire going, and prepare yourselves for a pair of nasal-based horror stories that will frighten your Jingle Bells off!
Our first tale of nostril terror comes all the way from southern India, where a 13-year-old boy jumped into a water well to cool off. Hey, southern India gets hot, even in November. But like something out of a bad sci-fi movie, his peaceful swim was interrupted when something swam up his nose, causing him extreme pain. After a 30-minute procedure, the doctor pulled out the culprit: A horrific alien parasite! Okay, we’re lying; it was a fish. But we had you going, didn’t we?
Well, maybe that didn’t get you frightened. But we have more rhinal dread to share! A young girl in Las Vegas stuck a pair of plastic doll shoes up her nose, one in each nostril. Her mother removed one shoe, but neither she nor urgent care could reach the second. A trip to the hospital was in order, and once there, the doctors were able to remove the foreign object in seconds.
But as with all things in U.S. medicine, a reckoning would soon come. You feel it now, the dread in this woman’s heart when the hospital bill came.
She takes the envelope, and opens it slowly.
The paper unfolds, rough and heavy in her hands.
Her eyes scan the page, looking for the number, where is it, where is it? It must be here, it must be ...
$3,000.
That’s right, for this simple procedure, performed with a pair of fancy tweezers, the hospital saw fit to charge the hapless mother $3,000! AHHHHHHHHHHHH!
Some say that the mother’s high-deductible insurance policy reduced the cost to $1,700. But we ask you, does that make the story any less spooky? We think not.
Hoverboarding down the root canal
Time spent in the dentist’s chair is among the most anxiety-inducing in anyone’s life. The needles. The grinding. The drilling. The rinsing. The spitting. The throbbing copays.
But you know what might inject a few cc’s of fun into your oral hygiene visits?
Did you guess ... a hoverboard?
If you did, well, you’re probably dentist Steve Martin in “Little Shop of Horrors.” Or perhaps Alaska dentist Seth Lookhart, who authorities say performed a tooth extraction on a sedated patient while Dr. Lookhart also rode a hoverboard. There are also charges of felony Medicaid fraud and reckless endangerment. And allegations of hefty theft from his practice partners. Oh, and a state board apparently suspended Dr. Lookhart’s dental license in 2017.
But hey, pulling teeth while taming a hoverboard? Photos or it didn’t happen, right?
Unfortunately for the well-balanced dentist, there are photos. Actually, there’s an entire video. And when prosecutors showed it to Dr. Lookhart’s unwitting and horrified costar, she was about as happy as the impacted wisdom teeth your teen kid’s still toting around.
Dr. Lookhart denied the felony fraud charges. But he did cop to the hoverboard. Which puts him one up on his cinematic “Wild and Crazy Guy” doppelganger. Even as a neurosurgeon in “The Man With Two Brains,” Mr. Martin never attempted to hoverboard while performing double “cranial screw-top” brain surgeries.
CSI: Quebec
They may live in that eternally polite land on the other side of our northern border, but they know where the bodies are buried. Lots of bodies. Some of them in shallow graves. Some of them in vehicles.
No, we are not talking about Gil Grissom and the gang at CSI. We’re talking about the Secure Site for Research in Thanatology, also known as the “body farm,” which is scheduled to open this spring in Becancour, Quebec.
It’s the first such outdoor forensic facility in Canada and the first in the world – there are also body farms in the United States, Australia, and the Netherlands – to be located in a northern climate.
“We’re particularly interested in understanding what happens when a body is in subzero temperatures, when there’s a lot of snow on the ground, and how that freeze and then the thaw process might actually change the rate of decomposition,” Shari Forbes, the farm’s director, told CTV News recently.
The science team will be out on the farm every day, meticulously checking each body – talk about making a list and checking it twice – for all the important CSI stuff: how long fingerprints and DNA evidence last, the effects of insect feeding and egg-laying, and the ability of dogs to detect scents.
The decomposition process in a cold climate will be a strange and wondrous journey, and the body farm’s work can, perhaps, best be summed up by none other than Mr. Grissom, who once said that getting to the evidence means having to destroy the evidence.
Then again, he also said that “dead men don’t ride roller coasters,” so the analogy only goes so far.
A cure for nosiness
Christmas may be just around the corner, but is there ever really a wrong time to huddle around a campfire and swap scary stories? So bundle up, get the fire going, and prepare yourselves for a pair of nasal-based horror stories that will frighten your Jingle Bells off!
Our first tale of nostril terror comes all the way from southern India, where a 13-year-old boy jumped into a water well to cool off. Hey, southern India gets hot, even in November. But like something out of a bad sci-fi movie, his peaceful swim was interrupted when something swam up his nose, causing him extreme pain. After a 30-minute procedure, the doctor pulled out the culprit: A horrific alien parasite! Okay, we’re lying; it was a fish. But we had you going, didn’t we?
Well, maybe that didn’t get you frightened. But we have more rhinal dread to share! A young girl in Las Vegas stuck a pair of plastic doll shoes up her nose, one in each nostril. Her mother removed one shoe, but neither she nor urgent care could reach the second. A trip to the hospital was in order, and once there, the doctors were able to remove the foreign object in seconds.
But as with all things in U.S. medicine, a reckoning would soon come. You feel it now, the dread in this woman’s heart when the hospital bill came.
She takes the envelope, and opens it slowly.
The paper unfolds, rough and heavy in her hands.
Her eyes scan the page, looking for the number, where is it, where is it? It must be here, it must be ...
$3,000.
That’s right, for this simple procedure, performed with a pair of fancy tweezers, the hospital saw fit to charge the hapless mother $3,000! AHHHHHHHHHHHH!
Some say that the mother’s high-deductible insurance policy reduced the cost to $1,700. But we ask you, does that make the story any less spooky? We think not.
Hoverboarding down the root canal
Time spent in the dentist’s chair is among the most anxiety-inducing in anyone’s life. The needles. The grinding. The drilling. The rinsing. The spitting. The throbbing copays.
But you know what might inject a few cc’s of fun into your oral hygiene visits?
Did you guess ... a hoverboard?
If you did, well, you’re probably dentist Steve Martin in “Little Shop of Horrors.” Or perhaps Alaska dentist Seth Lookhart, who authorities say performed a tooth extraction on a sedated patient while Dr. Lookhart also rode a hoverboard. There are also charges of felony Medicaid fraud and reckless endangerment. And allegations of hefty theft from his practice partners. Oh, and a state board apparently suspended Dr. Lookhart’s dental license in 2017.
But hey, pulling teeth while taming a hoverboard? Photos or it didn’t happen, right?
Unfortunately for the well-balanced dentist, there are photos. Actually, there’s an entire video. And when prosecutors showed it to Dr. Lookhart’s unwitting and horrified costar, she was about as happy as the impacted wisdom teeth your teen kid’s still toting around.
Dr. Lookhart denied the felony fraud charges. But he did cop to the hoverboard. Which puts him one up on his cinematic “Wild and Crazy Guy” doppelganger. Even as a neurosurgeon in “The Man With Two Brains,” Mr. Martin never attempted to hoverboard while performing double “cranial screw-top” brain surgeries.
CSI: Quebec
They may live in that eternally polite land on the other side of our northern border, but they know where the bodies are buried. Lots of bodies. Some of them in shallow graves. Some of them in vehicles.
No, we are not talking about Gil Grissom and the gang at CSI. We’re talking about the Secure Site for Research in Thanatology, also known as the “body farm,” which is scheduled to open this spring in Becancour, Quebec.
It’s the first such outdoor forensic facility in Canada and the first in the world – there are also body farms in the United States, Australia, and the Netherlands – to be located in a northern climate.
“We’re particularly interested in understanding what happens when a body is in subzero temperatures, when there’s a lot of snow on the ground, and how that freeze and then the thaw process might actually change the rate of decomposition,” Shari Forbes, the farm’s director, told CTV News recently.
The science team will be out on the farm every day, meticulously checking each body – talk about making a list and checking it twice – for all the important CSI stuff: how long fingerprints and DNA evidence last, the effects of insect feeding and egg-laying, and the ability of dogs to detect scents.
The decomposition process in a cold climate will be a strange and wondrous journey, and the body farm’s work can, perhaps, best be summed up by none other than Mr. Grissom, who once said that getting to the evidence means having to destroy the evidence.
Then again, he also said that “dead men don’t ride roller coasters,” so the analogy only goes so far.
Novel agent boosts adjuvant therapy for high-risk breast cancer
SAN ANTONIO – For postoperative breast cancer patients with a high risk of recurrence, the oral fluoropyrimidine-based drug S-1 could boost benefits of standard adjuvant treatment, based on results from the Japanese phase 3 POTENT trial.
Adding S-1 to endocrine therapy increased 5-year invasive disease-free survival (iDFS) by approximately 5% among patients with hormone receptor (HR)–positive, HER2-negative breast cancer, reported lead author Masakazu Toi, MD, PhD, of Kyoto University Hospital in Japan, and colleagues.
S-1 is a combination drug based on a biochemical modification of fluorouracil, with components aimed at potentiating activity and reducing gastrointestinal toxicity, Dr. Toi said at the San Antonio Breast Cancer Symposium.
Session moderator Carlos Arteaga, MD, of the University of Texas, Dallas, said that standard adjuvant treatment for breast cancer may evolve over the next few years, with S-1 representing one of several novel approaches currently under investigation.
“We’re all trying to optimize adjuvant endocrine therapy for patients that need it,” Dr. Arteaga said. “One approach is to add chemotherapy for those with a high-risk recurrence score. The other one is to … use CDK4/6 inhibitors in addition to endocrine therapy. … Clearly, endocrine therapy works in a majority of patients but in some it’s not sufficient, and we need to add a second intervention—that could be chemo in some cases, or it could be CDK4/6 inhibitors, if those trials pan out. This is another [strategy].”
The open-label POTENT trial was conducted at 139 centers in Japan, involving 1,932 patients with stage I-IIIB HR-positive, HER2-negative postoperative breast cancer who had intermediate to high risk of recurrence. Patients were enrolled within 1 year of surgery and 6 months of starting adjuvant therapy.
Patients were randomized at a 1:1 ratio to receive either standard endocrine therapy or endocrine therapy plus S-1, with S-1 given on a 2-weeks-on/1-week-off basis for 1 year. The primary endpoint was iDFS, defined as time from randomization to invasive disease recurrence, occurrence of second invasive cancer event, or death
After a median follow-up of 51.4 months, iDFS events were significantly more common in the control arm than the S-1 arm (15.9% vs. 10.6%; hazard ratio, 0.63; P = .0003). This translated to an estimated 5-year iDFS of 81.5% among patients who received endocrine therapy alone versus 86.9% among patients who also received S-1 (P less than .001).
While adding S-1 to endocrine therapy did increase the rate of adverse events, most instances were mild, leading the investigators to describe the novel regimen as “well tolerated and manageable.”
Among severe adverse events, grade 3-4 diarrhea and neutropenia were significantly more common in the S-1 arm than the control arm, with diarrhea occurring at a rate of 1.9% versus 0%, respectively, and neutropenia occurring at a rate of 7.5% versus 0.7%, respectively.
Based on these findings, Dr. Toi concluded that adding S-1 could be a viable option for improving outcomes in select patients.
“Our findings support the addition of S-1 to standard endocrine therapy in the postoperative adjuvant setting for patients with HR-positive/HER2-negative disease and an intermediate or higher risk of recurrence,” Dr. Toi said.
But according to invited discussant Priyanka Sharma, MD, of the University of Kansas, Kansas City, a place for S-1 in the clinic remains to be seen, partially because of potential differences in fluoropyrimidine drug metabolism based on ethnic background.
“The POTENT trial design does not allow us to discern in which setting and patient population addition of S-1 is most meaningful,” Dr. Sharma said. “This trial was done in Japan, so efficacy and toxicity in a non-Asian population is unclear.”
The study was funded by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation and Taiho Pharmaceutical. The investigators reported additional relationships with Bristol-Myers Squibb, Daiichi Sankyo, Genomic Health, and others.
SOURCE: Toi M et al. SABCS 2019, Abstract GS1-09.
SAN ANTONIO – For postoperative breast cancer patients with a high risk of recurrence, the oral fluoropyrimidine-based drug S-1 could boost benefits of standard adjuvant treatment, based on results from the Japanese phase 3 POTENT trial.
Adding S-1 to endocrine therapy increased 5-year invasive disease-free survival (iDFS) by approximately 5% among patients with hormone receptor (HR)–positive, HER2-negative breast cancer, reported lead author Masakazu Toi, MD, PhD, of Kyoto University Hospital in Japan, and colleagues.
S-1 is a combination drug based on a biochemical modification of fluorouracil, with components aimed at potentiating activity and reducing gastrointestinal toxicity, Dr. Toi said at the San Antonio Breast Cancer Symposium.
Session moderator Carlos Arteaga, MD, of the University of Texas, Dallas, said that standard adjuvant treatment for breast cancer may evolve over the next few years, with S-1 representing one of several novel approaches currently under investigation.
“We’re all trying to optimize adjuvant endocrine therapy for patients that need it,” Dr. Arteaga said. “One approach is to add chemotherapy for those with a high-risk recurrence score. The other one is to … use CDK4/6 inhibitors in addition to endocrine therapy. … Clearly, endocrine therapy works in a majority of patients but in some it’s not sufficient, and we need to add a second intervention—that could be chemo in some cases, or it could be CDK4/6 inhibitors, if those trials pan out. This is another [strategy].”
The open-label POTENT trial was conducted at 139 centers in Japan, involving 1,932 patients with stage I-IIIB HR-positive, HER2-negative postoperative breast cancer who had intermediate to high risk of recurrence. Patients were enrolled within 1 year of surgery and 6 months of starting adjuvant therapy.
Patients were randomized at a 1:1 ratio to receive either standard endocrine therapy or endocrine therapy plus S-1, with S-1 given on a 2-weeks-on/1-week-off basis for 1 year. The primary endpoint was iDFS, defined as time from randomization to invasive disease recurrence, occurrence of second invasive cancer event, or death
After a median follow-up of 51.4 months, iDFS events were significantly more common in the control arm than the S-1 arm (15.9% vs. 10.6%; hazard ratio, 0.63; P = .0003). This translated to an estimated 5-year iDFS of 81.5% among patients who received endocrine therapy alone versus 86.9% among patients who also received S-1 (P less than .001).
While adding S-1 to endocrine therapy did increase the rate of adverse events, most instances were mild, leading the investigators to describe the novel regimen as “well tolerated and manageable.”
Among severe adverse events, grade 3-4 diarrhea and neutropenia were significantly more common in the S-1 arm than the control arm, with diarrhea occurring at a rate of 1.9% versus 0%, respectively, and neutropenia occurring at a rate of 7.5% versus 0.7%, respectively.
Based on these findings, Dr. Toi concluded that adding S-1 could be a viable option for improving outcomes in select patients.
“Our findings support the addition of S-1 to standard endocrine therapy in the postoperative adjuvant setting for patients with HR-positive/HER2-negative disease and an intermediate or higher risk of recurrence,” Dr. Toi said.
But according to invited discussant Priyanka Sharma, MD, of the University of Kansas, Kansas City, a place for S-1 in the clinic remains to be seen, partially because of potential differences in fluoropyrimidine drug metabolism based on ethnic background.
“The POTENT trial design does not allow us to discern in which setting and patient population addition of S-1 is most meaningful,” Dr. Sharma said. “This trial was done in Japan, so efficacy and toxicity in a non-Asian population is unclear.”
The study was funded by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation and Taiho Pharmaceutical. The investigators reported additional relationships with Bristol-Myers Squibb, Daiichi Sankyo, Genomic Health, and others.
SOURCE: Toi M et al. SABCS 2019, Abstract GS1-09.
SAN ANTONIO – For postoperative breast cancer patients with a high risk of recurrence, the oral fluoropyrimidine-based drug S-1 could boost benefits of standard adjuvant treatment, based on results from the Japanese phase 3 POTENT trial.
Adding S-1 to endocrine therapy increased 5-year invasive disease-free survival (iDFS) by approximately 5% among patients with hormone receptor (HR)–positive, HER2-negative breast cancer, reported lead author Masakazu Toi, MD, PhD, of Kyoto University Hospital in Japan, and colleagues.
S-1 is a combination drug based on a biochemical modification of fluorouracil, with components aimed at potentiating activity and reducing gastrointestinal toxicity, Dr. Toi said at the San Antonio Breast Cancer Symposium.
Session moderator Carlos Arteaga, MD, of the University of Texas, Dallas, said that standard adjuvant treatment for breast cancer may evolve over the next few years, with S-1 representing one of several novel approaches currently under investigation.
“We’re all trying to optimize adjuvant endocrine therapy for patients that need it,” Dr. Arteaga said. “One approach is to add chemotherapy for those with a high-risk recurrence score. The other one is to … use CDK4/6 inhibitors in addition to endocrine therapy. … Clearly, endocrine therapy works in a majority of patients but in some it’s not sufficient, and we need to add a second intervention—that could be chemo in some cases, or it could be CDK4/6 inhibitors, if those trials pan out. This is another [strategy].”
The open-label POTENT trial was conducted at 139 centers in Japan, involving 1,932 patients with stage I-IIIB HR-positive, HER2-negative postoperative breast cancer who had intermediate to high risk of recurrence. Patients were enrolled within 1 year of surgery and 6 months of starting adjuvant therapy.
Patients were randomized at a 1:1 ratio to receive either standard endocrine therapy or endocrine therapy plus S-1, with S-1 given on a 2-weeks-on/1-week-off basis for 1 year. The primary endpoint was iDFS, defined as time from randomization to invasive disease recurrence, occurrence of second invasive cancer event, or death
After a median follow-up of 51.4 months, iDFS events were significantly more common in the control arm than the S-1 arm (15.9% vs. 10.6%; hazard ratio, 0.63; P = .0003). This translated to an estimated 5-year iDFS of 81.5% among patients who received endocrine therapy alone versus 86.9% among patients who also received S-1 (P less than .001).
While adding S-1 to endocrine therapy did increase the rate of adverse events, most instances were mild, leading the investigators to describe the novel regimen as “well tolerated and manageable.”
Among severe adverse events, grade 3-4 diarrhea and neutropenia were significantly more common in the S-1 arm than the control arm, with diarrhea occurring at a rate of 1.9% versus 0%, respectively, and neutropenia occurring at a rate of 7.5% versus 0.7%, respectively.
Based on these findings, Dr. Toi concluded that adding S-1 could be a viable option for improving outcomes in select patients.
“Our findings support the addition of S-1 to standard endocrine therapy in the postoperative adjuvant setting for patients with HR-positive/HER2-negative disease and an intermediate or higher risk of recurrence,” Dr. Toi said.
But according to invited discussant Priyanka Sharma, MD, of the University of Kansas, Kansas City, a place for S-1 in the clinic remains to be seen, partially because of potential differences in fluoropyrimidine drug metabolism based on ethnic background.
“The POTENT trial design does not allow us to discern in which setting and patient population addition of S-1 is most meaningful,” Dr. Sharma said. “This trial was done in Japan, so efficacy and toxicity in a non-Asian population is unclear.”
The study was funded by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation and Taiho Pharmaceutical. The investigators reported additional relationships with Bristol-Myers Squibb, Daiichi Sankyo, Genomic Health, and others.
SOURCE: Toi M et al. SABCS 2019, Abstract GS1-09.
REPORTING FROM SABCS 2019
New ASH guideline: VTE prophylaxis after major surgery
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
EXPERT ANALYSIS FROM ASH 2019
Failed ATEMPT: T-DM1 no safer in early HER2+ breast cancer
SAN ANTONIO – Nice try, ATEMPT investigators, but trastuzumab emtansine (T-DM1) does not have a disease-free survival or safety advantage over paclitaxel plus trastuzumab in the adjuvant setting for patients with stage 1 HER2-positive breast cancer.
For 497 patients randomized on a 3:1 basis to receive either T-DM1 every 3 weeks for 17 cycles or paclitaxel plus trastuzumab (TH) weekly for 12 cycles followed by trastuzumab every 3 weeks for an additional 13 cycles, there were no significant between-regimen differences in the co-primary endpoints of 3-year disease-free survival (DFS) or clinically relevant toxicities, reported Sara M. Tolaney, MD, MPH of Dana-Farber Cancer Institute, Boston.
“While there was no difference in the overall incidence of clinically relevant toxicities between the two arms, there were differences in the toxicity profiles that were seen between T-DM1 and TH. It’s also important to know that not all toxicities that are significant for our patients are captured in this clinically relevant toxicity endpoint, such as alopecia, and patient-reported outcomes should be considered when assessing the tolerability of therapy,” she said at the San Antonio Breast Cancer Symposium.
For patients with stage 1, HER2-positive breast cancer at high risk of recurrence, paclitaxel and trastuzumab is associated with a 93% disease survival rate.
T-DM1, an drug antibody conjugate of trastuzumab and DM1, a cytotoxic agent, is active against metastatic HER2-positive breast cancer and in patients with residual disease after neoadjuvant HER2-directed therapy.
“Importantly, T-DM1 has been associated with less toxicity when compared to chemotherapy with trastuzumab,” said Dr. Tolaney.
To see whether T-DM1 could be a less toxic treatment option for patients with stage 1 HER2-positive breast cancer at risk for recurrence, the investigators enrolled 512 patients who were within 90 days of surgery, had N0 or microscopic N1 disease, left ventricular ejection fraction (LVEF) of 50% or greater, and no prior invasive breast cancer.
The patients were stratified by age (younger than 55 or 55 and older), planned radiation (yes or no), and planned hormonal therapy (yes or no), and then randomly assigned on a 3:1 basis to receive either T-DM1 3.6 mg/kg intravenously every 3 weeks for 17 cycles, or TH, consisting of paclitaxel 80 mg/m2 plus trastuzumab 2 mg/kg intravenously weekly for 12 cycles, followed by trastuzumab 6 mg/kg every 3 weeks for an additional 13 cycles.
A total of 383 patients assigned to T-DM1 and 114 assigned to TH were included in the intention-to-treat analysis.
The study arms were well balanced by tumor size, histologic grade, hormone receptor status, and HER2 status by fluorescent in situ hybridization (1+, 2+, 3+ or not performed).
Three-year disease-free survival with was 97.7% with T-DM1 and 93.2% with TH, but the study was not powered to detect efficacy differences between the two adjuvant regimens, Dr. Tolaney noted.
In all, 46% of patients in each arm had clinically relevant toxicities. Grade 3 or greater nonhematologic toxicities were seen in 10% of those on T-DM1, vs. 11% of those on TH. Grade 2 or greater neurotoxicity was seen in 11% of patients and 23%, respectively.
Four patients on T-DM1 had grade 4 hematologic toxicity vs. none on TH. Febrile neutropenia was not seen among patients on T-DM1, but occurred in two patients on TH.
The incidence of toxicity requiring a dose delay was 28% and 26%, respectively, while nearly 3 times as many patients on T-DM1 had toxicities requiring early discontinuation (17% vs. 6%).
T-DM1 was also associated with higher incidences of grade 2 or greater thrombocytopenia (11% vs. 1%), alanine aminotransferase elevation (9% vs. 4%), and bilirubin increase (5% vs. 1%).
Three patients on T-DM1 and one on TH had symptomatic heart failure. Asymptomatic declines in LVEF were seen in five and seven patients, respectively.
“Given the low event rate seen in this trial, T-DM1 may be considered an alternative treatment approach to TH for select patients with stage 1 HER2-positive disease who are concerned about specific TH-related side effects and who understand the potential for T-DM1 toxicities. There may be some patients and physicians, however, who will want longer follow-up before adopting such an approach,” Dr. Tolaney said.
In the question and response session, an audience member said, “I would like to add one more toxicity that has not been considered, which is financial toxicity. There’s a huge difference in the price of both regimens, and the total cost of care.”
Dr. Tolaney replied that “certainly we did consider this and we had our pharmacist do some calculations looking at this financial toxicity, and it is true that a year of T-DM1 does cost a little more than two times as much as TH.”
She agreed that financial toxicity is a very important consideration when making treatment decisions, “but I think there are differences in toxicity profiles that do need to be considered when making individual decisions for our patients.”
Invited discussant A. Jo Chien, MD of the University of California, San Francisco noted that 75% of all patients enrolled in ATEMPT had hormone receptor positive disease “and therefore 3 years median follow-up is relatively short for this cohort.
“Due to the high rates of discontinuation in the T-DM1 arm, it is important to remember that duration of toxicity is a contributor to overall tolerability, which often is not well characterized by standard toxicity assessments, which often just report highest-grade toxicity at one point in time. High-grade toxicities that are short-lived may be acceptable, but low-grade toxicities for longer duration may not,” she said.
The ATEMPT trial was funded by Genentech. Dr. Tolaney has disclosed advisory board participation, institutional research funds, honoraria, and travel expense reimbursement from the company. Dr. Chien disclosed institutional research funding from Merck, Puma, Seattle Genetics, Astellas, and Amgen.
SOURCE: Tolaney SM et al. SABCS 2019, Abstract GS1-05.
SAN ANTONIO – Nice try, ATEMPT investigators, but trastuzumab emtansine (T-DM1) does not have a disease-free survival or safety advantage over paclitaxel plus trastuzumab in the adjuvant setting for patients with stage 1 HER2-positive breast cancer.
For 497 patients randomized on a 3:1 basis to receive either T-DM1 every 3 weeks for 17 cycles or paclitaxel plus trastuzumab (TH) weekly for 12 cycles followed by trastuzumab every 3 weeks for an additional 13 cycles, there were no significant between-regimen differences in the co-primary endpoints of 3-year disease-free survival (DFS) or clinically relevant toxicities, reported Sara M. Tolaney, MD, MPH of Dana-Farber Cancer Institute, Boston.
“While there was no difference in the overall incidence of clinically relevant toxicities between the two arms, there were differences in the toxicity profiles that were seen between T-DM1 and TH. It’s also important to know that not all toxicities that are significant for our patients are captured in this clinically relevant toxicity endpoint, such as alopecia, and patient-reported outcomes should be considered when assessing the tolerability of therapy,” she said at the San Antonio Breast Cancer Symposium.
For patients with stage 1, HER2-positive breast cancer at high risk of recurrence, paclitaxel and trastuzumab is associated with a 93% disease survival rate.
T-DM1, an drug antibody conjugate of trastuzumab and DM1, a cytotoxic agent, is active against metastatic HER2-positive breast cancer and in patients with residual disease after neoadjuvant HER2-directed therapy.
“Importantly, T-DM1 has been associated with less toxicity when compared to chemotherapy with trastuzumab,” said Dr. Tolaney.
To see whether T-DM1 could be a less toxic treatment option for patients with stage 1 HER2-positive breast cancer at risk for recurrence, the investigators enrolled 512 patients who were within 90 days of surgery, had N0 or microscopic N1 disease, left ventricular ejection fraction (LVEF) of 50% or greater, and no prior invasive breast cancer.
The patients were stratified by age (younger than 55 or 55 and older), planned radiation (yes or no), and planned hormonal therapy (yes or no), and then randomly assigned on a 3:1 basis to receive either T-DM1 3.6 mg/kg intravenously every 3 weeks for 17 cycles, or TH, consisting of paclitaxel 80 mg/m2 plus trastuzumab 2 mg/kg intravenously weekly for 12 cycles, followed by trastuzumab 6 mg/kg every 3 weeks for an additional 13 cycles.
A total of 383 patients assigned to T-DM1 and 114 assigned to TH were included in the intention-to-treat analysis.
The study arms were well balanced by tumor size, histologic grade, hormone receptor status, and HER2 status by fluorescent in situ hybridization (1+, 2+, 3+ or not performed).
Three-year disease-free survival with was 97.7% with T-DM1 and 93.2% with TH, but the study was not powered to detect efficacy differences between the two adjuvant regimens, Dr. Tolaney noted.
In all, 46% of patients in each arm had clinically relevant toxicities. Grade 3 or greater nonhematologic toxicities were seen in 10% of those on T-DM1, vs. 11% of those on TH. Grade 2 or greater neurotoxicity was seen in 11% of patients and 23%, respectively.
Four patients on T-DM1 had grade 4 hematologic toxicity vs. none on TH. Febrile neutropenia was not seen among patients on T-DM1, but occurred in two patients on TH.
The incidence of toxicity requiring a dose delay was 28% and 26%, respectively, while nearly 3 times as many patients on T-DM1 had toxicities requiring early discontinuation (17% vs. 6%).
T-DM1 was also associated with higher incidences of grade 2 or greater thrombocytopenia (11% vs. 1%), alanine aminotransferase elevation (9% vs. 4%), and bilirubin increase (5% vs. 1%).
Three patients on T-DM1 and one on TH had symptomatic heart failure. Asymptomatic declines in LVEF were seen in five and seven patients, respectively.
“Given the low event rate seen in this trial, T-DM1 may be considered an alternative treatment approach to TH for select patients with stage 1 HER2-positive disease who are concerned about specific TH-related side effects and who understand the potential for T-DM1 toxicities. There may be some patients and physicians, however, who will want longer follow-up before adopting such an approach,” Dr. Tolaney said.
In the question and response session, an audience member said, “I would like to add one more toxicity that has not been considered, which is financial toxicity. There’s a huge difference in the price of both regimens, and the total cost of care.”
Dr. Tolaney replied that “certainly we did consider this and we had our pharmacist do some calculations looking at this financial toxicity, and it is true that a year of T-DM1 does cost a little more than two times as much as TH.”
She agreed that financial toxicity is a very important consideration when making treatment decisions, “but I think there are differences in toxicity profiles that do need to be considered when making individual decisions for our patients.”
Invited discussant A. Jo Chien, MD of the University of California, San Francisco noted that 75% of all patients enrolled in ATEMPT had hormone receptor positive disease “and therefore 3 years median follow-up is relatively short for this cohort.
“Due to the high rates of discontinuation in the T-DM1 arm, it is important to remember that duration of toxicity is a contributor to overall tolerability, which often is not well characterized by standard toxicity assessments, which often just report highest-grade toxicity at one point in time. High-grade toxicities that are short-lived may be acceptable, but low-grade toxicities for longer duration may not,” she said.
The ATEMPT trial was funded by Genentech. Dr. Tolaney has disclosed advisory board participation, institutional research funds, honoraria, and travel expense reimbursement from the company. Dr. Chien disclosed institutional research funding from Merck, Puma, Seattle Genetics, Astellas, and Amgen.
SOURCE: Tolaney SM et al. SABCS 2019, Abstract GS1-05.
SAN ANTONIO – Nice try, ATEMPT investigators, but trastuzumab emtansine (T-DM1) does not have a disease-free survival or safety advantage over paclitaxel plus trastuzumab in the adjuvant setting for patients with stage 1 HER2-positive breast cancer.
For 497 patients randomized on a 3:1 basis to receive either T-DM1 every 3 weeks for 17 cycles or paclitaxel plus trastuzumab (TH) weekly for 12 cycles followed by trastuzumab every 3 weeks for an additional 13 cycles, there were no significant between-regimen differences in the co-primary endpoints of 3-year disease-free survival (DFS) or clinically relevant toxicities, reported Sara M. Tolaney, MD, MPH of Dana-Farber Cancer Institute, Boston.
“While there was no difference in the overall incidence of clinically relevant toxicities between the two arms, there were differences in the toxicity profiles that were seen between T-DM1 and TH. It’s also important to know that not all toxicities that are significant for our patients are captured in this clinically relevant toxicity endpoint, such as alopecia, and patient-reported outcomes should be considered when assessing the tolerability of therapy,” she said at the San Antonio Breast Cancer Symposium.
For patients with stage 1, HER2-positive breast cancer at high risk of recurrence, paclitaxel and trastuzumab is associated with a 93% disease survival rate.
T-DM1, an drug antibody conjugate of trastuzumab and DM1, a cytotoxic agent, is active against metastatic HER2-positive breast cancer and in patients with residual disease after neoadjuvant HER2-directed therapy.
“Importantly, T-DM1 has been associated with less toxicity when compared to chemotherapy with trastuzumab,” said Dr. Tolaney.
To see whether T-DM1 could be a less toxic treatment option for patients with stage 1 HER2-positive breast cancer at risk for recurrence, the investigators enrolled 512 patients who were within 90 days of surgery, had N0 or microscopic N1 disease, left ventricular ejection fraction (LVEF) of 50% or greater, and no prior invasive breast cancer.
The patients were stratified by age (younger than 55 or 55 and older), planned radiation (yes or no), and planned hormonal therapy (yes or no), and then randomly assigned on a 3:1 basis to receive either T-DM1 3.6 mg/kg intravenously every 3 weeks for 17 cycles, or TH, consisting of paclitaxel 80 mg/m2 plus trastuzumab 2 mg/kg intravenously weekly for 12 cycles, followed by trastuzumab 6 mg/kg every 3 weeks for an additional 13 cycles.
A total of 383 patients assigned to T-DM1 and 114 assigned to TH were included in the intention-to-treat analysis.
The study arms were well balanced by tumor size, histologic grade, hormone receptor status, and HER2 status by fluorescent in situ hybridization (1+, 2+, 3+ or not performed).
Three-year disease-free survival with was 97.7% with T-DM1 and 93.2% with TH, but the study was not powered to detect efficacy differences between the two adjuvant regimens, Dr. Tolaney noted.
In all, 46% of patients in each arm had clinically relevant toxicities. Grade 3 or greater nonhematologic toxicities were seen in 10% of those on T-DM1, vs. 11% of those on TH. Grade 2 or greater neurotoxicity was seen in 11% of patients and 23%, respectively.
Four patients on T-DM1 had grade 4 hematologic toxicity vs. none on TH. Febrile neutropenia was not seen among patients on T-DM1, but occurred in two patients on TH.
The incidence of toxicity requiring a dose delay was 28% and 26%, respectively, while nearly 3 times as many patients on T-DM1 had toxicities requiring early discontinuation (17% vs. 6%).
T-DM1 was also associated with higher incidences of grade 2 or greater thrombocytopenia (11% vs. 1%), alanine aminotransferase elevation (9% vs. 4%), and bilirubin increase (5% vs. 1%).
Three patients on T-DM1 and one on TH had symptomatic heart failure. Asymptomatic declines in LVEF were seen in five and seven patients, respectively.
“Given the low event rate seen in this trial, T-DM1 may be considered an alternative treatment approach to TH for select patients with stage 1 HER2-positive disease who are concerned about specific TH-related side effects and who understand the potential for T-DM1 toxicities. There may be some patients and physicians, however, who will want longer follow-up before adopting such an approach,” Dr. Tolaney said.
In the question and response session, an audience member said, “I would like to add one more toxicity that has not been considered, which is financial toxicity. There’s a huge difference in the price of both regimens, and the total cost of care.”
Dr. Tolaney replied that “certainly we did consider this and we had our pharmacist do some calculations looking at this financial toxicity, and it is true that a year of T-DM1 does cost a little more than two times as much as TH.”
She agreed that financial toxicity is a very important consideration when making treatment decisions, “but I think there are differences in toxicity profiles that do need to be considered when making individual decisions for our patients.”
Invited discussant A. Jo Chien, MD of the University of California, San Francisco noted that 75% of all patients enrolled in ATEMPT had hormone receptor positive disease “and therefore 3 years median follow-up is relatively short for this cohort.
“Due to the high rates of discontinuation in the T-DM1 arm, it is important to remember that duration of toxicity is a contributor to overall tolerability, which often is not well characterized by standard toxicity assessments, which often just report highest-grade toxicity at one point in time. High-grade toxicities that are short-lived may be acceptable, but low-grade toxicities for longer duration may not,” she said.
The ATEMPT trial was funded by Genentech. Dr. Tolaney has disclosed advisory board participation, institutional research funds, honoraria, and travel expense reimbursement from the company. Dr. Chien disclosed institutional research funding from Merck, Puma, Seattle Genetics, Astellas, and Amgen.
SOURCE: Tolaney SM et al. SABCS 2019, Abstract GS1-05.
REPORTING FROM SABCS 2019
Key clinical point: Trastuzumab emtansine did not have a lower incidence of toxicities compared with trastuzumab/paclitaxel.
Major finding: In each trial arm, 46% of patients had clinically relevant toxicities.
Study details: Randomized phase 2 trial in 497 patients with stage 1 HER2-positive breast cancer.
Disclosures: The ATEMPT trial was funded by Genentech. Dr. Tolaney has disclosed advisory board participation, institutional research funds, honoraria, and travel expense reimbursement from the company. Dr. Chien disclosed institutional research funding from Merck, Puma, Seattle Genetics, Astellas, and Amgen.
Source: Tolaney SM et al. SABCS 2019. Abstract GS1-05.
Abnormal gaze processing found in patients with bipolar disorder
Patients with bipolar disorder show altered gaze processing on EEG recordings taken during working memory exercises, new study results suggest.
The study, led by Cristina Berchio of the department of basic neurosciences at the University of Geneva, recruited 19 euthymic patients with bipolar I or II from the Mood Disorders Unit at the University Hospital of Geneva and 19 controls matched for age, gender, education level, and handedness. While undergoing high-density EEG recording, participants performed a two-back working memory exercise that involved neutral faces with either direct or averted gazes. The study was published in NeuroImage: Clinical.
; both of those functions are thought to be impaired in patients with bipolar disorder. They suggested that this might reflect early-life dysfunctional parental-infant gaze experiences that could affect how those patients with bipolar disorder learned emotion-regulation strategies. “In this sense, our early gaze experiences might also be considered an environmental risk factor, that might remain as a vulnerability trait in [bipolar patients],” they wrote.
Limitations of the study include the working memory exercise’s design, which could have led to misleading anticipatory effects. The small sample size is another limitation that affected the ability to perform certain analyses. The surface nature of EEG also limited evaluation of deeper brain structures that might have proved salient to this exercise.
The study was supported by several entities, including the Swiss National Center of Competence in Research. The authors declared no conflicts of interest.
SOURCE: Berchio C et al. NeuroImage Clin. 2019. doi: 10.1016/j.nicl.2017.09.006.
Patients with bipolar disorder show altered gaze processing on EEG recordings taken during working memory exercises, new study results suggest.
The study, led by Cristina Berchio of the department of basic neurosciences at the University of Geneva, recruited 19 euthymic patients with bipolar I or II from the Mood Disorders Unit at the University Hospital of Geneva and 19 controls matched for age, gender, education level, and handedness. While undergoing high-density EEG recording, participants performed a two-back working memory exercise that involved neutral faces with either direct or averted gazes. The study was published in NeuroImage: Clinical.
; both of those functions are thought to be impaired in patients with bipolar disorder. They suggested that this might reflect early-life dysfunctional parental-infant gaze experiences that could affect how those patients with bipolar disorder learned emotion-regulation strategies. “In this sense, our early gaze experiences might also be considered an environmental risk factor, that might remain as a vulnerability trait in [bipolar patients],” they wrote.
Limitations of the study include the working memory exercise’s design, which could have led to misleading anticipatory effects. The small sample size is another limitation that affected the ability to perform certain analyses. The surface nature of EEG also limited evaluation of deeper brain structures that might have proved salient to this exercise.
The study was supported by several entities, including the Swiss National Center of Competence in Research. The authors declared no conflicts of interest.
SOURCE: Berchio C et al. NeuroImage Clin. 2019. doi: 10.1016/j.nicl.2017.09.006.
Patients with bipolar disorder show altered gaze processing on EEG recordings taken during working memory exercises, new study results suggest.
The study, led by Cristina Berchio of the department of basic neurosciences at the University of Geneva, recruited 19 euthymic patients with bipolar I or II from the Mood Disorders Unit at the University Hospital of Geneva and 19 controls matched for age, gender, education level, and handedness. While undergoing high-density EEG recording, participants performed a two-back working memory exercise that involved neutral faces with either direct or averted gazes. The study was published in NeuroImage: Clinical.
; both of those functions are thought to be impaired in patients with bipolar disorder. They suggested that this might reflect early-life dysfunctional parental-infant gaze experiences that could affect how those patients with bipolar disorder learned emotion-regulation strategies. “In this sense, our early gaze experiences might also be considered an environmental risk factor, that might remain as a vulnerability trait in [bipolar patients],” they wrote.
Limitations of the study include the working memory exercise’s design, which could have led to misleading anticipatory effects. The small sample size is another limitation that affected the ability to perform certain analyses. The surface nature of EEG also limited evaluation of deeper brain structures that might have proved salient to this exercise.
The study was supported by several entities, including the Swiss National Center of Competence in Research. The authors declared no conflicts of interest.
SOURCE: Berchio C et al. NeuroImage Clin. 2019. doi: 10.1016/j.nicl.2017.09.006.
FROM NEUROIMAGE: CLINICAL
Pigmented lesion on face
While the lesion’s proximity to the eyelashes and lid margin made dermoscopy difficult, the physician was able to use a dermatoscope to view the lesion and recognize it as nodular basal cell carcinoma (BCC). (If dermoscopy had not been an option, a hand magnifier or otoscope could have been used to help with magnification and diagnosis.)
Nodular BCCs usually present with a raised pearly border, a central ulceration, and telangiectasias. In this case, the central erosion was much more obvious with dermoscopy. Also visible were abnormal telangiectasias around the central erosion; they were especially dilated and tortuous (referred to as an arborizing pattern) at the 4:00 position. The diagnosis was confirmed by a small tangential shave biopsy of the inferior aspect of the lesion.
BCCs are referred for Mohs micrographic surgery (MMS) when they are any of the following: in high-risk locations such as the T-zone of the face (eyes, nose, and mouth); > 2 cm in diameter; a recurrence of a previous BCC; or a high-risk type including infiltrating, morpheaform, or basosquamous (based on pathology). Lower risk nodular BCCs are usually treated with excision or electrodesiccation and curettage.
In this case, the BCC was in a high-risk location and required MMS. The challenge was that the lesion was so close to the lid margin that resection of the cancer and subsequent repair could lead to ectropion/poor lid closure. The Mohs surgeon resected the lesion in 3 stages. The oculoplastic surgeon then closed the defect via a multilayered repair.
Images and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
While the lesion’s proximity to the eyelashes and lid margin made dermoscopy difficult, the physician was able to use a dermatoscope to view the lesion and recognize it as nodular basal cell carcinoma (BCC). (If dermoscopy had not been an option, a hand magnifier or otoscope could have been used to help with magnification and diagnosis.)
Nodular BCCs usually present with a raised pearly border, a central ulceration, and telangiectasias. In this case, the central erosion was much more obvious with dermoscopy. Also visible were abnormal telangiectasias around the central erosion; they were especially dilated and tortuous (referred to as an arborizing pattern) at the 4:00 position. The diagnosis was confirmed by a small tangential shave biopsy of the inferior aspect of the lesion.
BCCs are referred for Mohs micrographic surgery (MMS) when they are any of the following: in high-risk locations such as the T-zone of the face (eyes, nose, and mouth); > 2 cm in diameter; a recurrence of a previous BCC; or a high-risk type including infiltrating, morpheaform, or basosquamous (based on pathology). Lower risk nodular BCCs are usually treated with excision or electrodesiccation and curettage.
In this case, the BCC was in a high-risk location and required MMS. The challenge was that the lesion was so close to the lid margin that resection of the cancer and subsequent repair could lead to ectropion/poor lid closure. The Mohs surgeon resected the lesion in 3 stages. The oculoplastic surgeon then closed the defect via a multilayered repair.
Images and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
While the lesion’s proximity to the eyelashes and lid margin made dermoscopy difficult, the physician was able to use a dermatoscope to view the lesion and recognize it as nodular basal cell carcinoma (BCC). (If dermoscopy had not been an option, a hand magnifier or otoscope could have been used to help with magnification and diagnosis.)
Nodular BCCs usually present with a raised pearly border, a central ulceration, and telangiectasias. In this case, the central erosion was much more obvious with dermoscopy. Also visible were abnormal telangiectasias around the central erosion; they were especially dilated and tortuous (referred to as an arborizing pattern) at the 4:00 position. The diagnosis was confirmed by a small tangential shave biopsy of the inferior aspect of the lesion.
BCCs are referred for Mohs micrographic surgery (MMS) when they are any of the following: in high-risk locations such as the T-zone of the face (eyes, nose, and mouth); > 2 cm in diameter; a recurrence of a previous BCC; or a high-risk type including infiltrating, morpheaform, or basosquamous (based on pathology). Lower risk nodular BCCs are usually treated with excision or electrodesiccation and curettage.
In this case, the BCC was in a high-risk location and required MMS. The challenge was that the lesion was so close to the lid margin that resection of the cancer and subsequent repair could lead to ectropion/poor lid closure. The Mohs surgeon resected the lesion in 3 stages. The oculoplastic surgeon then closed the defect via a multilayered repair.
Images and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
