Jessica Craig

A 2-mg/kg dosage of pembrolizumab given to adult patients with non–small-cell lung cancer (NSCLC) every 3 weeks is optimal to both reduce tumor size and avoid treatment-related adverse events, according to a new method of analysis.

Current methods for determining the maximum tolerated dose (MTD) based on dose-limiting toxicities may be outmoded for targeted therapies and immunotherapies, where the biologically effective dose (BED) may be much lower than the MTD.

“Using the MTD rather than the BED could expose patients to a higher dose than that necessary to achieve clinical effect and may increase toxicity, which could lower overall clinical effectiveness. Therefore, dose determination in oncology should use a multifactorial approach that includes not only clinical data from the first treatment cycle but extended clinical data, preclinical models, pharmacokinetics, pharmacodynamics, and integrated modeling and simulation,” said Dr. Manash Chatterjee of Merck, and associates (Ann Oncol. 2016 April 26. doi: 10.1093/annonc/mdw174).

Dr. Chatterjee and associates analyzed data from KEYNOTE-001 using various statistical and mathematical modeling techniques to determine the lowest effective drug dosage of pembrolizumab, a highly selective humanized IgG4 monoclonal antibody that targets the programmed death-1 receptor, for treatment of patients with NSCLC.

Patients enrolled in the KEYNOTE-001 trial received pembrolizumab at doses of 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression or intolerable toxicity, or until the patient or investigator decided to stop treatment. Sixty-one patients were treated with pembrolizumab at 2 mg/kg every 3 weeks, 287 patients were treated at 10 mg/kg every 3 weeks, and 202 patients were treated at 10 mg/kg every 2 weeks. PD-1 expression was assessed from biopsy samples using a prototype assay.

Decreases from baseline tumor size were observed for 67% of patients with known PD-L1 expression treated with pembrolizumab at 2 mg/kg every 3 weeks, 66% for patients treated at 10 mg/kg every 3 weeks, and 63% for patients treated at 10 mg/kg every 2 weeks.

Data on occurrence and severity of adverse events were collected throughout the study and up to 60 days after treatment was discontinued. Adverse events were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 4.0). Treatment-related adverse events were reported for 47% of patients treated at 2 mg/kg every 3 weeks. The frequency and severity of adverse events were similar for all dosages, the investigators reported.

Exposure-efficacy was evaluated by way of exploratory regression analyses followed by nonlinear mixed effects modeling. The model found no significant difference in the exposure-efficacy relationship based on dosage. PD-L1 expression and EGFR mutation were the only two factors that explained a significant portion of interindividual variability in tumor size decrease.

Exposure-safety was evaluated via logistic regression modeling where safety was defined as the frequency of adverse events. The model revealed that there was no significant relationship between adverse events and exposure to pembrolizumab or dosage. Overall duration of treatment was the only factor that was significantly related to adverse events.

“These results support the use of a 2-mg/kg Q3W dosage in patients with previously treated, advanced NSCLC,” the investigators concluded.

jcraig@frontlinemedcom.com

On Twitter@jess_craig94

A 2-mg/kg dosage of pembrolizumab given to adult patients with non–small-cell lung cancer (NSCLC) every 3 weeks is optimal to both reduce tumor size and avoid treatment-related adverse events, according to a new method of analysis.

Current methods for determining the maximum tolerated dose (MTD) based on dose-limiting toxicities may be outmoded for targeted therapies and immunotherapies, where the biologically effective dose (BED) may be much lower than the MTD.

“Using the MTD rather than the BED could expose patients to a higher dose than that necessary to achieve clinical effect and may increase toxicity, which could lower overall clinical effectiveness. Therefore, dose determination in oncology should use a multifactorial approach that includes not only clinical data from the first treatment cycle but extended clinical data, preclinical models, pharmacokinetics, pharmacodynamics, and integrated modeling and simulation,” said Dr. Manash Chatterjee of Merck, and associates (Ann Oncol. 2016 April 26. doi: 10.1093/annonc/mdw174).

Dr. Chatterjee and associates analyzed data from KEYNOTE-001 using various statistical and mathematical modeling techniques to determine the lowest effective drug dosage of pembrolizumab, a highly selective humanized IgG4 monoclonal antibody that targets the programmed death-1 receptor, for treatment of patients with NSCLC.

Patients enrolled in the KEYNOTE-001 trial received pembrolizumab at doses of 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression or intolerable toxicity, or until the patient or investigator decided to stop treatment. Sixty-one patients were treated with pembrolizumab at 2 mg/kg every 3 weeks, 287 patients were treated at 10 mg/kg every 3 weeks, and 202 patients were treated at 10 mg/kg every 2 weeks. PD-1 expression was assessed from biopsy samples using a prototype assay.

Decreases from baseline tumor size were observed for 67% of patients with known PD-L1 expression treated with pembrolizumab at 2 mg/kg every 3 weeks, 66% for patients treated at 10 mg/kg every 3 weeks, and 63% for patients treated at 10 mg/kg every 2 weeks.

Data on occurrence and severity of adverse events were collected throughout the study and up to 60 days after treatment was discontinued. Adverse events were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 4.0). Treatment-related adverse events were reported for 47% of patients treated at 2 mg/kg every 3 weeks. The frequency and severity of adverse events were similar for all dosages, the investigators reported.

Exposure-efficacy was evaluated by way of exploratory regression analyses followed by nonlinear mixed effects modeling. The model found no significant difference in the exposure-efficacy relationship based on dosage. PD-L1 expression and EGFR mutation were the only two factors that explained a significant portion of interindividual variability in tumor size decrease.

Exposure-safety was evaluated via logistic regression modeling where safety was defined as the frequency of adverse events. The model revealed that there was no significant relationship between adverse events and exposure to pembrolizumab or dosage. Overall duration of treatment was the only factor that was significantly related to adverse events.

“These results support the use of a 2-mg/kg Q3W dosage in patients with previously treated, advanced NSCLC,” the investigators concluded.

jcraig@frontlinemedcom.com

On Twitter@jess_craig94

A 2-mg/kg dosage of pembrolizumab given to adult patients with non–small-cell lung cancer (NSCLC) every 3 weeks is optimal to both reduce tumor size and avoid treatment-related adverse events, according to a new method of analysis.

Current methods for determining the maximum tolerated dose (MTD) based on dose-limiting toxicities may be outmoded for targeted therapies and immunotherapies, where the biologically effective dose (BED) may be much lower than the MTD.

“Using the MTD rather than the BED could expose patients to a higher dose than that necessary to achieve clinical effect and may increase toxicity, which could lower overall clinical effectiveness. Therefore, dose determination in oncology should use a multifactorial approach that includes not only clinical data from the first treatment cycle but extended clinical data, preclinical models, pharmacokinetics, pharmacodynamics, and integrated modeling and simulation,” said Dr. Manash Chatterjee of Merck, and associates (Ann Oncol. 2016 April 26. doi: 10.1093/annonc/mdw174).

Dr. Chatterjee and associates analyzed data from KEYNOTE-001 using various statistical and mathematical modeling techniques to determine the lowest effective drug dosage of pembrolizumab, a highly selective humanized IgG4 monoclonal antibody that targets the programmed death-1 receptor, for treatment of patients with NSCLC.

Patients enrolled in the KEYNOTE-001 trial received pembrolizumab at doses of 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression or intolerable toxicity, or until the patient or investigator decided to stop treatment. Sixty-one patients were treated with pembrolizumab at 2 mg/kg every 3 weeks, 287 patients were treated at 10 mg/kg every 3 weeks, and 202 patients were treated at 10 mg/kg every 2 weeks. PD-1 expression was assessed from biopsy samples using a prototype assay.

Decreases from baseline tumor size were observed for 67% of patients with known PD-L1 expression treated with pembrolizumab at 2 mg/kg every 3 weeks, 66% for patients treated at 10 mg/kg every 3 weeks, and 63% for patients treated at 10 mg/kg every 2 weeks.

Data on occurrence and severity of adverse events were collected throughout the study and up to 60 days after treatment was discontinued. Adverse events were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 4.0). Treatment-related adverse events were reported for 47% of patients treated at 2 mg/kg every 3 weeks. The frequency and severity of adverse events were similar for all dosages, the investigators reported.

Exposure-efficacy was evaluated by way of exploratory regression analyses followed by nonlinear mixed effects modeling. The model found no significant difference in the exposure-efficacy relationship based on dosage. PD-L1 expression and EGFR mutation were the only two factors that explained a significant portion of interindividual variability in tumor size decrease.

Exposure-safety was evaluated via logistic regression modeling where safety was defined as the frequency of adverse events. The model revealed that there was no significant relationship between adverse events and exposure to pembrolizumab or dosage. Overall duration of treatment was the only factor that was significantly related to adverse events.

“These results support the use of a 2-mg/kg Q3W dosage in patients with previously treated, advanced NSCLC,” the investigators concluded.

jcraig@frontlinemedcom.com

On Twitter@jess_craig94

The Molecular Immunology Center is a campus of concrete and stone buildings with dark-tinted windows set against palm trees and pink tropical flowers. The buildings are imposing and seem to stretch endlessly along the flat terrain of Havana, Cuba. The research institute, like most buildings in Cuba, is just a few minutes’ walk to the Atlantic Ocean coastline. Inside the research and development building, investigators are working on creating 18 new cancer immunotherapy treatments from vaccines to monoclonal antibodies to synthetic cytokines. A few buildings down, in an almost 50,000–square foot manufacturing plant, a positive pressure air gradient system whirs, and stirred tank bioreactors clank in continuous motion. It is here that the CIMAvax-EGF, a therapeutic vaccine used to treat non–small-cell lung cancer (NSCLC), is manufactured, formulated, and packaged into 40-L sterile bulk bags.

©Konstik/Thinkstock

The Molecular Immunology Center, also called the Center of Molecular Immunology or Centro de Immunologia Molecular, was founded in the early 1990’s and the research that eventually led to CIMAvax-EGF began almost immediately, spurred by Cuba’s high rate of lung cancer–related deaths (at the time the second leading cause of death and the leading cause of cancer mortality in the country).

The vaccine works by stimulating a patient’s own immune system to make antibodies against epidermal growth factor (EGF), which depletes circulating EGF levels and prevents EGF from binding to its receptor. “The epidermal growth factor receptor (EGFR) is a well-known oncogene. Its overactivation can induce malignant transformation of a normal cell, signaling inhibition of apoptosis, cell proliferation, angiogenesis, metastasis, and tumor-induced proinflammatory and immunosuppressive processes,” wrote Dr. Pedro Rodríguez and his associates at the Molecular Immunology Center in Cuba (MEDICC Rev. 2010;12:17-23).

“The EGFR signaling and transduction pathway can be efficiently interrupted by EGF deprivation, direct specific mAb [monoclonal antibody] receptor inhibition, or low-molecular-weight molecules competing intracellularly with adenosine triphosphate for the receptor’s tyrosine kinase activity site, with negative repercussions on cell proliferation and, consequently, on tumor development. Inducing EGF deprivation by active immunotherapy is an emerging concept developed by Cuban researchers that involves manipulating an individual’s immune response to release its own effector antibodies against EGF, thereby reducing tumor size or preventing its progression,” the investigators wrote.

Early preclinical studies for vaccine formulation began in Cuba in 1992. Over the next few years, researchers perfected the vaccine’s formula: EGF along with two immunopotentiating molecules, an adjuvant called Montanide ISA 51 and the virulent protein P64k from the microbial organism Neisseria meningitidis (Ann Oncol. 1998;9:431-5; Ann Oncol. 2003;14:461-6).

Together, the adjuvant and the virulent protein activate the immune system while the overabundance of EGF in the body directs antibodies to be made specifically against EGF and not virulent protein P64k. Although some antibodies bind the EGF introduced by the vaccine, other antibodies target cancerous cells where EGFR is overexpressed.

NSCLC was selected “because of its frequency and because EGFR is overexpressed in tissues during development and progression of lung neoplasms,” reported the investigators.

Subsequent clinical trials focused on fine-tuning administration route, dose, dosing interval, optimal combinations with other established therapies, and reducing vaccine-related side effects, which include fever, chills, nausea, headache, asthenia, and tremor.

Researchers found that administering the vaccine in “high but fractioned dose[s] in multiple anatomical sites (such as the 2 deltoid and 2 gluteal regions), thereby bringing the EGF vaccine closer to regional lymph nodes and synergizing the immune response” resulted in the best patient outcomes. In addition, significantly better patient outcomes were achieved when the vaccine was administered before and after chemotherapy.

By 1995, Cuban researchers had successfully completed five separate phase I/II clinical trials and one phase II clinical trial.

Pooling the results from the various clinical trials, non–small-cell lung cancer patients who received the vaccine and who were under the age of 60, lived an average of 4-6 months longer than patients who did not receive the vaccine or were older than 60.

By 2009 “more than 700 patients [had] received the vaccine over the years, many of them in seven clinical trials in Cuba, Canada, and the U.K.,” reported an online Cuban newspaper, Cuba Headlines.

It wasn’t until September 2011 that Cuban researchers officially began distributing the vaccine to Cuban citizens.

“The drug could turn the cancer into a manageable, chronic disease by generating antibodies against the proteins, which triggered the uncontrolled cell proliferation,” Dr. Gisela Gonzalez of the Center of Molecular Immunology said in an interview in 2009 following the official launch of the vaccine.

Today, ongoing clinical trials continue in Cuba and are also underway (at various stages) in several other countries, including the United States. The vaccine still has a long way to go before it can be hailed as a true “cancer cure,” a sentiment that many American publications expressed and one that the researchers at Roswell Park Cancer Institute who are leading the U.S. clinical trials are vehemently trying to quell. Nonetheless, the now global reach of CIMAvax may mark a promising paradigm shift in the field of oncology.

jcraig@frontlinemedcom.com

On Twitter @jess_craig94

The Molecular Immunology Center is a campus of concrete and stone buildings with dark-tinted windows set against palm trees and pink tropical flowers. The buildings are imposing and seem to stretch endlessly along the flat terrain of Havana, Cuba. The research institute, like most buildings in Cuba, is just a few minutes’ walk to the Atlantic Ocean coastline. Inside the research and development building, investigators are working on creating 18 new cancer immunotherapy treatments from vaccines to monoclonal antibodies to synthetic cytokines. A few buildings down, in an almost 50,000–square foot manufacturing plant, a positive pressure air gradient system whirs, and stirred tank bioreactors clank in continuous motion. It is here that the CIMAvax-EGF, a therapeutic vaccine used to treat non–small-cell lung cancer (NSCLC), is manufactured, formulated, and packaged into 40-L sterile bulk bags.

©Konstik/Thinkstock

The Molecular Immunology Center, also called the Center of Molecular Immunology or Centro de Immunologia Molecular, was founded in the early 1990’s and the research that eventually led to CIMAvax-EGF began almost immediately, spurred by Cuba’s high rate of lung cancer–related deaths (at the time the second leading cause of death and the leading cause of cancer mortality in the country).

The vaccine works by stimulating a patient’s own immune system to make antibodies against epidermal growth factor (EGF), which depletes circulating EGF levels and prevents EGF from binding to its receptor. “The epidermal growth factor receptor (EGFR) is a well-known oncogene. Its overactivation can induce malignant transformation of a normal cell, signaling inhibition of apoptosis, cell proliferation, angiogenesis, metastasis, and tumor-induced proinflammatory and immunosuppressive processes,” wrote Dr. Pedro Rodríguez and his associates at the Molecular Immunology Center in Cuba (MEDICC Rev. 2010;12:17-23).

“The EGFR signaling and transduction pathway can be efficiently interrupted by EGF deprivation, direct specific mAb [monoclonal antibody] receptor inhibition, or low-molecular-weight molecules competing intracellularly with adenosine triphosphate for the receptor’s tyrosine kinase activity site, with negative repercussions on cell proliferation and, consequently, on tumor development. Inducing EGF deprivation by active immunotherapy is an emerging concept developed by Cuban researchers that involves manipulating an individual’s immune response to release its own effector antibodies against EGF, thereby reducing tumor size or preventing its progression,” the investigators wrote.

Early preclinical studies for vaccine formulation began in Cuba in 1992. Over the next few years, researchers perfected the vaccine’s formula: EGF along with two immunopotentiating molecules, an adjuvant called Montanide ISA 51 and the virulent protein P64k from the microbial organism Neisseria meningitidis (Ann Oncol. 1998;9:431-5; Ann Oncol. 2003;14:461-6).

Together, the adjuvant and the virulent protein activate the immune system while the overabundance of EGF in the body directs antibodies to be made specifically against EGF and not virulent protein P64k. Although some antibodies bind the EGF introduced by the vaccine, other antibodies target cancerous cells where EGFR is overexpressed.

NSCLC was selected “because of its frequency and because EGFR is overexpressed in tissues during development and progression of lung neoplasms,” reported the investigators.

Subsequent clinical trials focused on fine-tuning administration route, dose, dosing interval, optimal combinations with other established therapies, and reducing vaccine-related side effects, which include fever, chills, nausea, headache, asthenia, and tremor.

Researchers found that administering the vaccine in “high but fractioned dose[s] in multiple anatomical sites (such as the 2 deltoid and 2 gluteal regions), thereby bringing the EGF vaccine closer to regional lymph nodes and synergizing the immune response” resulted in the best patient outcomes. In addition, significantly better patient outcomes were achieved when the vaccine was administered before and after chemotherapy.

By 1995, Cuban researchers had successfully completed five separate phase I/II clinical trials and one phase II clinical trial.

Pooling the results from the various clinical trials, non–small-cell lung cancer patients who received the vaccine and who were under the age of 60, lived an average of 4-6 months longer than patients who did not receive the vaccine or were older than 60.

By 2009 “more than 700 patients [had] received the vaccine over the years, many of them in seven clinical trials in Cuba, Canada, and the U.K.,” reported an online Cuban newspaper, Cuba Headlines.

It wasn’t until September 2011 that Cuban researchers officially began distributing the vaccine to Cuban citizens.

“The drug could turn the cancer into a manageable, chronic disease by generating antibodies against the proteins, which triggered the uncontrolled cell proliferation,” Dr. Gisela Gonzalez of the Center of Molecular Immunology said in an interview in 2009 following the official launch of the vaccine.

Today, ongoing clinical trials continue in Cuba and are also underway (at various stages) in several other countries, including the United States. The vaccine still has a long way to go before it can be hailed as a true “cancer cure,” a sentiment that many American publications expressed and one that the researchers at Roswell Park Cancer Institute who are leading the U.S. clinical trials are vehemently trying to quell. Nonetheless, the now global reach of CIMAvax may mark a promising paradigm shift in the field of oncology.

jcraig@frontlinemedcom.com

On Twitter @jess_craig94

The Molecular Immunology Center is a campus of concrete and stone buildings with dark-tinted windows set against palm trees and pink tropical flowers. The buildings are imposing and seem to stretch endlessly along the flat terrain of Havana, Cuba. The research institute, like most buildings in Cuba, is just a few minutes’ walk to the Atlantic Ocean coastline. Inside the research and development building, investigators are working on creating 18 new cancer immunotherapy treatments from vaccines to monoclonal antibodies to synthetic cytokines. A few buildings down, in an almost 50,000–square foot manufacturing plant, a positive pressure air gradient system whirs, and stirred tank bioreactors clank in continuous motion. It is here that the CIMAvax-EGF, a therapeutic vaccine used to treat non–small-cell lung cancer (NSCLC), is manufactured, formulated, and packaged into 40-L sterile bulk bags.

©Konstik/Thinkstock

The Molecular Immunology Center, also called the Center of Molecular Immunology or Centro de Immunologia Molecular, was founded in the early 1990’s and the research that eventually led to CIMAvax-EGF began almost immediately, spurred by Cuba’s high rate of lung cancer–related deaths (at the time the second leading cause of death and the leading cause of cancer mortality in the country).

The vaccine works by stimulating a patient’s own immune system to make antibodies against epidermal growth factor (EGF), which depletes circulating EGF levels and prevents EGF from binding to its receptor. “The epidermal growth factor receptor (EGFR) is a well-known oncogene. Its overactivation can induce malignant transformation of a normal cell, signaling inhibition of apoptosis, cell proliferation, angiogenesis, metastasis, and tumor-induced proinflammatory and immunosuppressive processes,” wrote Dr. Pedro Rodríguez and his associates at the Molecular Immunology Center in Cuba (MEDICC Rev. 2010;12:17-23).

“The EGFR signaling and transduction pathway can be efficiently interrupted by EGF deprivation, direct specific mAb [monoclonal antibody] receptor inhibition, or low-molecular-weight molecules competing intracellularly with adenosine triphosphate for the receptor’s tyrosine kinase activity site, with negative repercussions on cell proliferation and, consequently, on tumor development. Inducing EGF deprivation by active immunotherapy is an emerging concept developed by Cuban researchers that involves manipulating an individual’s immune response to release its own effector antibodies against EGF, thereby reducing tumor size or preventing its progression,” the investigators wrote.

Early preclinical studies for vaccine formulation began in Cuba in 1992. Over the next few years, researchers perfected the vaccine’s formula: EGF along with two immunopotentiating molecules, an adjuvant called Montanide ISA 51 and the virulent protein P64k from the microbial organism Neisseria meningitidis (Ann Oncol. 1998;9:431-5; Ann Oncol. 2003;14:461-6).

Together, the adjuvant and the virulent protein activate the immune system while the overabundance of EGF in the body directs antibodies to be made specifically against EGF and not virulent protein P64k. Although some antibodies bind the EGF introduced by the vaccine, other antibodies target cancerous cells where EGFR is overexpressed.

NSCLC was selected “because of its frequency and because EGFR is overexpressed in tissues during development and progression of lung neoplasms,” reported the investigators.

Subsequent clinical trials focused on fine-tuning administration route, dose, dosing interval, optimal combinations with other established therapies, and reducing vaccine-related side effects, which include fever, chills, nausea, headache, asthenia, and tremor.

Researchers found that administering the vaccine in “high but fractioned dose[s] in multiple anatomical sites (such as the 2 deltoid and 2 gluteal regions), thereby bringing the EGF vaccine closer to regional lymph nodes and synergizing the immune response” resulted in the best patient outcomes. In addition, significantly better patient outcomes were achieved when the vaccine was administered before and after chemotherapy.

By 1995, Cuban researchers had successfully completed five separate phase I/II clinical trials and one phase II clinical trial.

Pooling the results from the various clinical trials, non–small-cell lung cancer patients who received the vaccine and who were under the age of 60, lived an average of 4-6 months longer than patients who did not receive the vaccine or were older than 60.

By 2009 “more than 700 patients [had] received the vaccine over the years, many of them in seven clinical trials in Cuba, Canada, and the U.K.,” reported an online Cuban newspaper, Cuba Headlines.

It wasn’t until September 2011 that Cuban researchers officially began distributing the vaccine to Cuban citizens.

“The drug could turn the cancer into a manageable, chronic disease by generating antibodies against the proteins, which triggered the uncontrolled cell proliferation,” Dr. Gisela Gonzalez of the Center of Molecular Immunology said in an interview in 2009 following the official launch of the vaccine.

Today, ongoing clinical trials continue in Cuba and are also underway (at various stages) in several other countries, including the United States. The vaccine still has a long way to go before it can be hailed as a true “cancer cure,” a sentiment that many American publications expressed and one that the researchers at Roswell Park Cancer Institute who are leading the U.S. clinical trials are vehemently trying to quell. Nonetheless, the now global reach of CIMAvax may mark a promising paradigm shift in the field of oncology.

jcraig@frontlinemedcom.com

On Twitter @jess_craig94

Chemoradiotherapy does not improve overall or progression-free survival in patients with advanced pancreatic cancer, compared with chemotherapy alone. Gemcitabine plus erlotinib also does not improve overall or progression-free survival when compared with patients who received only gemcitabine.

“This open-label, randomized clinical trial showed no survival benefit of chemoradiotherapy compared with chemotherapy in patients with locally advanced pancreatic cancer... the addition of erlotinib to gemcitabine, despite excellent adherence (92%), failed to improve survival and yet was associated with increased grade 3 hematologic, digestive, and skin toxicities,” wrote Dr. Pascal Hammel of Beaujon Hospital, France, and associates (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4324).

“This suggests that in patients with locally advanced pancreatic cancer, more efficient systemic treatments are needed to treat any early micrometastatic spread and to downstage tumors,” they said.

Investigators enrolled 449 patients with advanced pancreatic cancer in the international, LAP07 phase III trial; 442 met the demographic criteria and were randomly divided into two groups, 223 of which received gemcitabine and 219 of which received gemcitabine plus erlotinib, during the first of two randomization steps. Patients in both groups received their designated drug regime intravenously for three weeks followed by a one week resting period for a total of four cycles.

During step one, 135 of the 223 patients who received gemcitabine, and 134 of the 219 patients who received gemcitabine plus erlotinib, survived the 16-week period progression free and were eligible for step two randomization; 136 patients were then randomly selected to receive chemotherapy and 133 patients were randomly selected to receive chemoradiotherapy.

After the two randomization steps, 68 patients received gemcitabine with chemotherapy, 68 patients received gemcitabine plus erlotinib with chemotherapy, 67 patients received gemcitabine with chemoradiotherapy, and 66 patients received gemcitabine plus erlotinib with chemoradiotherapy.

By the end of the clinical trial, 379 patients had died and 385 had experienced tumor progression. There was no significant difference in overall survival between patients receiving gemcitabine or gemcitabine plus erlotinib (hazard ratio, 1.19; 95% confidence interval, 0.97-1.45; P = .09), and there was no significant difference in progression-free survival (HR, 1.12; 95% CI, 0.92-1.36; P = .26). Patients who received erlotinib were at a significantly elevated risk for experiencing anemia, neutropenia, diarrhea, and acneiform rash when compared with patients who did not receive erlotinib.

There was no significant difference in overall survival between patients receiving chemotherapy or chemoradiotherapy (HR, 1.03; 95% CI, 0.79-1.34; P = .83), and there was no significant difference in progression-free survival (HR, .78; 95% CI, 0.61-1.01; P = .06).

There was also no significant difference in survival when first-step randomization status was combined with second-randomization status (P = .24).

This study was supported by Roche and the French National Institute of Cancer. Dr. Hammel reported receiving consulting fees from Celgene. Seven of the other thirteen investigators reported receiving personal fees, nonfinancial support, grant support, personal fees, or honoraria from Amgen, Merck Serono, Eli Lilly, Roche, Celgene, Sanofi, Novartis, Integragen, Eisai, Invectys, or Nestle.

jcraig@frontlinemedcom.com

On Twitter @jess_craig94

Chemoradiotherapy does not improve overall or progression-free survival in patients with advanced pancreatic cancer, compared with chemotherapy alone. Gemcitabine plus erlotinib also does not improve overall or progression-free survival when compared with patients who received only gemcitabine.

“This open-label, randomized clinical trial showed no survival benefit of chemoradiotherapy compared with chemotherapy in patients with locally advanced pancreatic cancer... the addition of erlotinib to gemcitabine, despite excellent adherence (92%), failed to improve survival and yet was associated with increased grade 3 hematologic, digestive, and skin toxicities,” wrote Dr. Pascal Hammel of Beaujon Hospital, France, and associates (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4324).

“This suggests that in patients with locally advanced pancreatic cancer, more efficient systemic treatments are needed to treat any early micrometastatic spread and to downstage tumors,” they said.

Investigators enrolled 449 patients with advanced pancreatic cancer in the international, LAP07 phase III trial; 442 met the demographic criteria and were randomly divided into two groups, 223 of which received gemcitabine and 219 of which received gemcitabine plus erlotinib, during the first of two randomization steps. Patients in both groups received their designated drug regime intravenously for three weeks followed by a one week resting period for a total of four cycles.

During step one, 135 of the 223 patients who received gemcitabine, and 134 of the 219 patients who received gemcitabine plus erlotinib, survived the 16-week period progression free and were eligible for step two randomization; 136 patients were then randomly selected to receive chemotherapy and 133 patients were randomly selected to receive chemoradiotherapy.

After the two randomization steps, 68 patients received gemcitabine with chemotherapy, 68 patients received gemcitabine plus erlotinib with chemotherapy, 67 patients received gemcitabine with chemoradiotherapy, and 66 patients received gemcitabine plus erlotinib with chemoradiotherapy.

By the end of the clinical trial, 379 patients had died and 385 had experienced tumor progression. There was no significant difference in overall survival between patients receiving gemcitabine or gemcitabine plus erlotinib (hazard ratio, 1.19; 95% confidence interval, 0.97-1.45; P = .09), and there was no significant difference in progression-free survival (HR, 1.12; 95% CI, 0.92-1.36; P = .26). Patients who received erlotinib were at a significantly elevated risk for experiencing anemia, neutropenia, diarrhea, and acneiform rash when compared with patients who did not receive erlotinib.

There was no significant difference in overall survival between patients receiving chemotherapy or chemoradiotherapy (HR, 1.03; 95% CI, 0.79-1.34; P = .83), and there was no significant difference in progression-free survival (HR, .78; 95% CI, 0.61-1.01; P = .06).

There was also no significant difference in survival when first-step randomization status was combined with second-randomization status (P = .24).

This study was supported by Roche and the French National Institute of Cancer. Dr. Hammel reported receiving consulting fees from Celgene. Seven of the other thirteen investigators reported receiving personal fees, nonfinancial support, grant support, personal fees, or honoraria from Amgen, Merck Serono, Eli Lilly, Roche, Celgene, Sanofi, Novartis, Integragen, Eisai, Invectys, or Nestle.

jcraig@frontlinemedcom.com

On Twitter @jess_craig94

Chemoradiotherapy does not improve overall or progression-free survival in patients with advanced pancreatic cancer, compared with chemotherapy alone. Gemcitabine plus erlotinib also does not improve overall or progression-free survival when compared with patients who received only gemcitabine.

“This open-label, randomized clinical trial showed no survival benefit of chemoradiotherapy compared with chemotherapy in patients with locally advanced pancreatic cancer... the addition of erlotinib to gemcitabine, despite excellent adherence (92%), failed to improve survival and yet was associated with increased grade 3 hematologic, digestive, and skin toxicities,” wrote Dr. Pascal Hammel of Beaujon Hospital, France, and associates (JAMA. 2016 May 3. doi: 10.1001/jama.2016.4324).

“This suggests that in patients with locally advanced pancreatic cancer, more efficient systemic treatments are needed to treat any early micrometastatic spread and to downstage tumors,” they said.

Investigators enrolled 449 patients with advanced pancreatic cancer in the international, LAP07 phase III trial; 442 met the demographic criteria and were randomly divided into two groups, 223 of which received gemcitabine and 219 of which received gemcitabine plus erlotinib, during the first of two randomization steps. Patients in both groups received their designated drug regime intravenously for three weeks followed by a one week resting period for a total of four cycles.

During step one, 135 of the 223 patients who received gemcitabine, and 134 of the 219 patients who received gemcitabine plus erlotinib, survived the 16-week period progression free and were eligible for step two randomization; 136 patients were then randomly selected to receive chemotherapy and 133 patients were randomly selected to receive chemoradiotherapy.

After the two randomization steps, 68 patients received gemcitabine with chemotherapy, 68 patients received gemcitabine plus erlotinib with chemotherapy, 67 patients received gemcitabine with chemoradiotherapy, and 66 patients received gemcitabine plus erlotinib with chemoradiotherapy.

By the end of the clinical trial, 379 patients had died and 385 had experienced tumor progression. There was no significant difference in overall survival between patients receiving gemcitabine or gemcitabine plus erlotinib (hazard ratio, 1.19; 95% confidence interval, 0.97-1.45; P = .09), and there was no significant difference in progression-free survival (HR, 1.12; 95% CI, 0.92-1.36; P = .26). Patients who received erlotinib were at a significantly elevated risk for experiencing anemia, neutropenia, diarrhea, and acneiform rash when compared with patients who did not receive erlotinib.

There was no significant difference in overall survival between patients receiving chemotherapy or chemoradiotherapy (HR, 1.03; 95% CI, 0.79-1.34; P = .83), and there was no significant difference in progression-free survival (HR, .78; 95% CI, 0.61-1.01; P = .06).

There was also no significant difference in survival when first-step randomization status was combined with second-randomization status (P = .24).

This study was supported by Roche and the French National Institute of Cancer. Dr. Hammel reported receiving consulting fees from Celgene. Seven of the other thirteen investigators reported receiving personal fees, nonfinancial support, grant support, personal fees, or honoraria from Amgen, Merck Serono, Eli Lilly, Roche, Celgene, Sanofi, Novartis, Integragen, Eisai, Invectys, or Nestle.

jcraig@frontlinemedcom.com

On Twitter @jess_craig94

Racial disparities in survival rates among young patients exist for those diagnosed with both early-stage and late-state colorectal cancer (CRC), investigators have found.

A review of Surveillance, Epidemiology, and End Results (SEER) data on young-onset CRC incidence and mortality rates showed that overall and cancer-specific survival rates were significantly lower for non-Hispanic black (NHB) patients when compared with non-Hispanic white (NHW) and Hispanic patients, reported Dr. Andreana Holowatyi of Wayne State University, Detroit, and her associates.

“Study of patients with young-onset CRC offers an opportunity to examine differences in cancer-specific survival by race, minimizing the potential impact that routine CRC screening among individuals 50 years of age and older might have on CRC-related outcomes,” the authors wrote (J Clin Oncol. 2016 May 2. doi: 10.1200/JCO.2015.65.0994).

The authors reviewed SEER data on 28,145 men and women aged 20-49 years at the time of CRC diagnosis. The sample included 19,497 NHWs, 4,384 NHBs, and 4,264 Hispanic patients and excluded patients who were diagnosed with cancer upon autopsy, patients who survived less than 2 months post diagnosis, and patients who were diagnosed with histopathologic subtypes other than adenocarcinoma. Patients diagnosed with any other type of cancer prior to their CRC diagnoses were excluded from survival analysis.

Stratification of patients by tumor stage and site showed that NHB patients were at an increased risk of cancer-specific death from colon cancers diagnosed at every stage, with the greatest differences observed among those with stage II cancers (hazard ratio, 1.69; 95% confidence interval, 1.33-2.14; P less than .001).

NHB patients were more likely to have CRCs of the proximal colon, compared with NHW and Hispanic patients (39.9% vs. 30.3% vs. 30.7% respectively; P less than .001) and more likely to have more advanced stage cancer. In addition, the NHB subpopulation included a significantly higher percentage of women, compared with NHW and Hispanic patients (50.3% vs. 45.8% vs. 46.3%, P less than .001).

In Cox proportional hazard models controlling for age, sex, race, county-level poverty, tumor stage, surgical intervention, and radiation therapy, Dr. Holowatyi and her associates found that NHB patients had significantly higher risk of cancer-specific death in colon cancers (HR, 1.35; 95% CI 1.26 to 1.45; P less than .001) and rectum/rectosigmoid junction cancers (HR, 1.51; 95% CI 1.37 to 1.68; P less than .001), compared with NHWs. Similar findings were reported for risk of overall death.

“Further studies of the clinical and molecular characteristics of young-onset CRCs are needed to explore potential tumor/treatment interactions associated with racial differences in survival and to refine clinical algorithms for CRC treatment and early detection,” the authors wrote.

This study was supported by funding from the Cancer Biology Graduate Program at Wayne State University, the National Cancer Institute, and an Epidemiology Core and National Institutes of Health Center grant. The authors did not have any disclosures to report.

jcraig@frontlinemedcom.com

Racial disparities in survival rates among young patients exist for those diagnosed with both early-stage and late-state colorectal cancer (CRC), investigators have found.

A review of Surveillance, Epidemiology, and End Results (SEER) data on young-onset CRC incidence and mortality rates showed that overall and cancer-specific survival rates were significantly lower for non-Hispanic black (NHB) patients when compared with non-Hispanic white (NHW) and Hispanic patients, reported Dr. Andreana Holowatyi of Wayne State University, Detroit, and her associates.

“Study of patients with young-onset CRC offers an opportunity to examine differences in cancer-specific survival by race, minimizing the potential impact that routine CRC screening among individuals 50 years of age and older might have on CRC-related outcomes,” the authors wrote (J Clin Oncol. 2016 May 2. doi: 10.1200/JCO.2015.65.0994).

The authors reviewed SEER data on 28,145 men and women aged 20-49 years at the time of CRC diagnosis. The sample included 19,497 NHWs, 4,384 NHBs, and 4,264 Hispanic patients and excluded patients who were diagnosed with cancer upon autopsy, patients who survived less than 2 months post diagnosis, and patients who were diagnosed with histopathologic subtypes other than adenocarcinoma. Patients diagnosed with any other type of cancer prior to their CRC diagnoses were excluded from survival analysis.

Stratification of patients by tumor stage and site showed that NHB patients were at an increased risk of cancer-specific death from colon cancers diagnosed at every stage, with the greatest differences observed among those with stage II cancers (hazard ratio, 1.69; 95% confidence interval, 1.33-2.14; P less than .001).

NHB patients were more likely to have CRCs of the proximal colon, compared with NHW and Hispanic patients (39.9% vs. 30.3% vs. 30.7% respectively; P less than .001) and more likely to have more advanced stage cancer. In addition, the NHB subpopulation included a significantly higher percentage of women, compared with NHW and Hispanic patients (50.3% vs. 45.8% vs. 46.3%, P less than .001).

In Cox proportional hazard models controlling for age, sex, race, county-level poverty, tumor stage, surgical intervention, and radiation therapy, Dr. Holowatyi and her associates found that NHB patients had significantly higher risk of cancer-specific death in colon cancers (HR, 1.35; 95% CI 1.26 to 1.45; P less than .001) and rectum/rectosigmoid junction cancers (HR, 1.51; 95% CI 1.37 to 1.68; P less than .001), compared with NHWs. Similar findings were reported for risk of overall death.

“Further studies of the clinical and molecular characteristics of young-onset CRCs are needed to explore potential tumor/treatment interactions associated with racial differences in survival and to refine clinical algorithms for CRC treatment and early detection,” the authors wrote.

This study was supported by funding from the Cancer Biology Graduate Program at Wayne State University, the National Cancer Institute, and an Epidemiology Core and National Institutes of Health Center grant. The authors did not have any disclosures to report.

jcraig@frontlinemedcom.com

Racial disparities in survival rates among young patients exist for those diagnosed with both early-stage and late-state colorectal cancer (CRC), investigators have found.

A review of Surveillance, Epidemiology, and End Results (SEER) data on young-onset CRC incidence and mortality rates showed that overall and cancer-specific survival rates were significantly lower for non-Hispanic black (NHB) patients when compared with non-Hispanic white (NHW) and Hispanic patients, reported Dr. Andreana Holowatyi of Wayne State University, Detroit, and her associates.

“Study of patients with young-onset CRC offers an opportunity to examine differences in cancer-specific survival by race, minimizing the potential impact that routine CRC screening among individuals 50 years of age and older might have on CRC-related outcomes,” the authors wrote (J Clin Oncol. 2016 May 2. doi: 10.1200/JCO.2015.65.0994).

The authors reviewed SEER data on 28,145 men and women aged 20-49 years at the time of CRC diagnosis. The sample included 19,497 NHWs, 4,384 NHBs, and 4,264 Hispanic patients and excluded patients who were diagnosed with cancer upon autopsy, patients who survived less than 2 months post diagnosis, and patients who were diagnosed with histopathologic subtypes other than adenocarcinoma. Patients diagnosed with any other type of cancer prior to their CRC diagnoses were excluded from survival analysis.

Stratification of patients by tumor stage and site showed that NHB patients were at an increased risk of cancer-specific death from colon cancers diagnosed at every stage, with the greatest differences observed among those with stage II cancers (hazard ratio, 1.69; 95% confidence interval, 1.33-2.14; P less than .001).

NHB patients were more likely to have CRCs of the proximal colon, compared with NHW and Hispanic patients (39.9% vs. 30.3% vs. 30.7% respectively; P less than .001) and more likely to have more advanced stage cancer. In addition, the NHB subpopulation included a significantly higher percentage of women, compared with NHW and Hispanic patients (50.3% vs. 45.8% vs. 46.3%, P less than .001).

In Cox proportional hazard models controlling for age, sex, race, county-level poverty, tumor stage, surgical intervention, and radiation therapy, Dr. Holowatyi and her associates found that NHB patients had significantly higher risk of cancer-specific death in colon cancers (HR, 1.35; 95% CI 1.26 to 1.45; P less than .001) and rectum/rectosigmoid junction cancers (HR, 1.51; 95% CI 1.37 to 1.68; P less than .001), compared with NHWs. Similar findings were reported for risk of overall death.

“Further studies of the clinical and molecular characteristics of young-onset CRCs are needed to explore potential tumor/treatment interactions associated with racial differences in survival and to refine clinical algorithms for CRC treatment and early detection,” the authors wrote.

This study was supported by funding from the Cancer Biology Graduate Program at Wayne State University, the National Cancer Institute, and an Epidemiology Core and National Institutes of Health Center grant. The authors did not have any disclosures to report.

jcraig@frontlinemedcom.com