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FDA approves nivolumab for patients with advanced melanoma
The Food and Drug Administration has approved the PD-1 inhibitor nivolumab for patients with unresectable or metastatic melanoma who no longer respond to other drugs.
Nivolumab, marketed as Opdivo, is intended for patients who have been previously treated with ipilimumab and, for patients whose tumors express a BRAF V600 mutation, for use after treatment with ipilimumab and a BRAF inhibitor, according to the FDA statement.
“Opdivo is the seventh new melanoma drug approved by the FDA since 2011,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research, said in the statement. “The continued development and approval of novel therapies based on our increasing understanding of tumor immunology and molecular pathways are changing the treatment paradigm for serious and life-threatening diseases.”
The FDA granted nivolumab breakthrough therapy designation and it was approved under the agency’s accelerated approval program.
Approval was based on CheckMate-037, a trial that demonstrated a 32% objective response rate with nivolumab vs. 11% with investigator’s choice chemotherapy among 120 patients with unresectable metastatic melanoma that progressed despite prior ipilimumab or a BRAF inhibitor, if BRAF mutation-positive.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
Opdivo is marketed by Bristol-Myers Squibb.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
On Twitter @NikolaidesLaura
The Food and Drug Administration has approved the PD-1 inhibitor nivolumab for patients with unresectable or metastatic melanoma who no longer respond to other drugs.
Nivolumab, marketed as Opdivo, is intended for patients who have been previously treated with ipilimumab and, for patients whose tumors express a BRAF V600 mutation, for use after treatment with ipilimumab and a BRAF inhibitor, according to the FDA statement.
“Opdivo is the seventh new melanoma drug approved by the FDA since 2011,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research, said in the statement. “The continued development and approval of novel therapies based on our increasing understanding of tumor immunology and molecular pathways are changing the treatment paradigm for serious and life-threatening diseases.”
The FDA granted nivolumab breakthrough therapy designation and it was approved under the agency’s accelerated approval program.
Approval was based on CheckMate-037, a trial that demonstrated a 32% objective response rate with nivolumab vs. 11% with investigator’s choice chemotherapy among 120 patients with unresectable metastatic melanoma that progressed despite prior ipilimumab or a BRAF inhibitor, if BRAF mutation-positive.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
Opdivo is marketed by Bristol-Myers Squibb.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
On Twitter @NikolaidesLaura
The Food and Drug Administration has approved the PD-1 inhibitor nivolumab for patients with unresectable or metastatic melanoma who no longer respond to other drugs.
Nivolumab, marketed as Opdivo, is intended for patients who have been previously treated with ipilimumab and, for patients whose tumors express a BRAF V600 mutation, for use after treatment with ipilimumab and a BRAF inhibitor, according to the FDA statement.
“Opdivo is the seventh new melanoma drug approved by the FDA since 2011,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research, said in the statement. “The continued development and approval of novel therapies based on our increasing understanding of tumor immunology and molecular pathways are changing the treatment paradigm for serious and life-threatening diseases.”
The FDA granted nivolumab breakthrough therapy designation and it was approved under the agency’s accelerated approval program.
Approval was based on CheckMate-037, a trial that demonstrated a 32% objective response rate with nivolumab vs. 11% with investigator’s choice chemotherapy among 120 patients with unresectable metastatic melanoma that progressed despite prior ipilimumab or a BRAF inhibitor, if BRAF mutation-positive.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
Opdivo is marketed by Bristol-Myers Squibb.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
On Twitter @NikolaidesLaura
FDA approves lanreotide for GEP-NETs after priority review
Lanreotide has been approved for the treatment of patients with unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
The Food and Drug Administration announced approval of the drug, marketed as Somatuline Depot by Ipsen Pharma on Dec. 16, following a priority, expedited review granted in September. Lanreotide was previously approved for the long-term treatment of acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option, according to the FDA statement.
The FDA based approval on results of the phase III CLARINET study, a randomized, double-blind, placebo-controlled trial evaluating lanreotide’s efficacy and safety in 204 patients with well or moderately differentiated, nonfunctioning GEP-NETs. Patients were randomized to receive either lanreotide 120 mg or placebo subcutaneously every 28 days.
Progression-free survival (PFS) was significantly longer in the lanreotide arm (hazard ratio, 0.47; P < .001). The median PFS in the lanreotide arm had not been reached at the time of the final analysis and will exceed 22 months, while the median PFS in the placebo arm was 16.6 months, the FDA reported in the statement.
Commonly reported adverse reactions in lanreotide-treated patients included abdominal pain, musculoskeletal pain, vomiting, headache, injection site reaction, hyperglycemia, hypertension, and cholelithiasis. The most common serious adverse reaction of lanreotide observed in CLARINET was vomiting (4%).
The recommended dose and schedule for lanreotide for GEP-NET is lanreotide 120 mg administered by deep subcutaneous injection every 28 days. Treatment should continue until disease progression or unacceptable toxicity, the FDA statement said.
On Twitter @nikolaideslaura
Lanreotide has been approved for the treatment of patients with unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
The Food and Drug Administration announced approval of the drug, marketed as Somatuline Depot by Ipsen Pharma on Dec. 16, following a priority, expedited review granted in September. Lanreotide was previously approved for the long-term treatment of acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option, according to the FDA statement.
The FDA based approval on results of the phase III CLARINET study, a randomized, double-blind, placebo-controlled trial evaluating lanreotide’s efficacy and safety in 204 patients with well or moderately differentiated, nonfunctioning GEP-NETs. Patients were randomized to receive either lanreotide 120 mg or placebo subcutaneously every 28 days.
Progression-free survival (PFS) was significantly longer in the lanreotide arm (hazard ratio, 0.47; P < .001). The median PFS in the lanreotide arm had not been reached at the time of the final analysis and will exceed 22 months, while the median PFS in the placebo arm was 16.6 months, the FDA reported in the statement.
Commonly reported adverse reactions in lanreotide-treated patients included abdominal pain, musculoskeletal pain, vomiting, headache, injection site reaction, hyperglycemia, hypertension, and cholelithiasis. The most common serious adverse reaction of lanreotide observed in CLARINET was vomiting (4%).
The recommended dose and schedule for lanreotide for GEP-NET is lanreotide 120 mg administered by deep subcutaneous injection every 28 days. Treatment should continue until disease progression or unacceptable toxicity, the FDA statement said.
On Twitter @nikolaideslaura
Lanreotide has been approved for the treatment of patients with unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
The Food and Drug Administration announced approval of the drug, marketed as Somatuline Depot by Ipsen Pharma on Dec. 16, following a priority, expedited review granted in September. Lanreotide was previously approved for the long-term treatment of acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option, according to the FDA statement.
The FDA based approval on results of the phase III CLARINET study, a randomized, double-blind, placebo-controlled trial evaluating lanreotide’s efficacy and safety in 204 patients with well or moderately differentiated, nonfunctioning GEP-NETs. Patients were randomized to receive either lanreotide 120 mg or placebo subcutaneously every 28 days.
Progression-free survival (PFS) was significantly longer in the lanreotide arm (hazard ratio, 0.47; P < .001). The median PFS in the lanreotide arm had not been reached at the time of the final analysis and will exceed 22 months, while the median PFS in the placebo arm was 16.6 months, the FDA reported in the statement.
Commonly reported adverse reactions in lanreotide-treated patients included abdominal pain, musculoskeletal pain, vomiting, headache, injection site reaction, hyperglycemia, hypertension, and cholelithiasis. The most common serious adverse reaction of lanreotide observed in CLARINET was vomiting (4%).
The recommended dose and schedule for lanreotide for GEP-NET is lanreotide 120 mg administered by deep subcutaneous injection every 28 days. Treatment should continue until disease progression or unacceptable toxicity, the FDA statement said.
On Twitter @nikolaideslaura
VIDEO: Multidisciplinary panel addresses role of anesthesia, analgesics in patient outcomes
SAN ANTONIO – A panel that included a breast surgeon, a medical oncologist, and a patient advocate met at the San Antonio Breast Cancer Symposium to discuss emerging research on the link between anesthesia and cancer recurrence. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.
Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.
The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @nikolaideslaura
SAN ANTONIO – A panel that included a breast surgeon, a medical oncologist, and a patient advocate met at the San Antonio Breast Cancer Symposium to discuss emerging research on the link between anesthesia and cancer recurrence. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.
Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.
The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @nikolaideslaura
SAN ANTONIO – A panel that included a breast surgeon, a medical oncologist, and a patient advocate met at the San Antonio Breast Cancer Symposium to discuss emerging research on the link between anesthesia and cancer recurrence. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.
Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.
The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @nikolaideslaura
AT SABCS 2014
VIDEO: Multidisciplinary panel addresses role of anesthesia, analgesics in patient outcomes
SAN ANTONIO – As follow-up to “Does choice of anesthesia set up your patient for metastasis?” published in the September issue, the Oncology Report brought together an anesthesiologist, a breast surgeon, a medical oncologist, and a patient advocate at the San Antonio Breast Cancer Symposium to further discuss the topic. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.
Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.
The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @nikolaideslaura
SAN ANTONIO – As follow-up to “Does choice of anesthesia set up your patient for metastasis?” published in the September issue, the Oncology Report brought together an anesthesiologist, a breast surgeon, a medical oncologist, and a patient advocate at the San Antonio Breast Cancer Symposium to further discuss the topic. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.
Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.
The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @nikolaideslaura
SAN ANTONIO – As follow-up to “Does choice of anesthesia set up your patient for metastasis?” published in the September issue, the Oncology Report brought together an anesthesiologist, a breast surgeon, a medical oncologist, and a patient advocate at the San Antonio Breast Cancer Symposium to further discuss the topic. The issue was first raised following publication of a retrospective study in 2006, which showed a 40% reduction in recurrence in women given a type of regional anesthesia, with general anesthesia, rather than general anesthesia and postoperative morphine anesthesia during primary breast cancer surgery.
Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, moderated the discussion with Dr. Juan Cata, assistant professor in the department of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, Dr. Susan Love, breast surgeon, and president and medical director of the Dr. Susan Love Research Foundation, and Musa Mayer, author and patient advocate.
The panel addressed the impact of surgery alone, anesthesia during surgery, and perioperative analgesics on patients’ immune functioning and ultimately disease outcomes. The state of the evidence in breast cancer and other tumor types, and an ongoing prospective trial with breast cancer patients, were also discussed.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @nikolaideslaura
AT SABCS 2014
ASH 2014 to highlight novel cancer therapies, longer follow-up results
Longer follow-up results on CAR-T therapy and early results from a novel BiTE therapy for patients with acute lymphoblastic leukemia, early results on checkpoint inhibitors to treat Hodgkin’s lymphoma, and phase III results on brentuximab vedotin to prevent recurrence of Hodgkin’s lymphoma will head up our onsite coverage of the American Society of Hematology Annual Meeting, to be held Dec. 6-9 in San Francisco.
Engineered T cells for treating patients with acute lymphoblastic leukemia
Reports on targeted therapies at ASH 2014 will include the latest follow-up of children with refractory acute lymphoblastic leukemia (ALL) who were treated with T-cells engineered with a chimeric antigen receptor targeting CD19, and results from a phase II study of blinatumomab, a bispecific T cell engager (BiTE) antibody construct, in patients with minimal residual disease B-precursor ALL.
Checkpoint inhibitors for treating patients with Hodgkin’s lymphoma
The first analyses from two studies using PD-1 antibodies for the treatment of classical Hodgkin’s lymphoma will be reported. Investigators will report phase I results of nivolumab in 23 heavily pretreated patients with classical HL, and of pembrolizumab (MK-3475) in 15 patients with classical HL with previously failed treatment using brentuximab vedotin.
Preventing recurrence of Hodgkin’s lymphoma
Highly anticipated results from the Aethera trial, a phase III study of brentuximab vedotin in 327 patients at risk of progression following autologous stem cell transplant for Hodgkin’s lymphoma, will also be reported.
On Twitter@nikolaideslaura
Longer follow-up results on CAR-T therapy and early results from a novel BiTE therapy for patients with acute lymphoblastic leukemia, early results on checkpoint inhibitors to treat Hodgkin’s lymphoma, and phase III results on brentuximab vedotin to prevent recurrence of Hodgkin’s lymphoma will head up our onsite coverage of the American Society of Hematology Annual Meeting, to be held Dec. 6-9 in San Francisco.
Engineered T cells for treating patients with acute lymphoblastic leukemia
Reports on targeted therapies at ASH 2014 will include the latest follow-up of children with refractory acute lymphoblastic leukemia (ALL) who were treated with T-cells engineered with a chimeric antigen receptor targeting CD19, and results from a phase II study of blinatumomab, a bispecific T cell engager (BiTE) antibody construct, in patients with minimal residual disease B-precursor ALL.
Checkpoint inhibitors for treating patients with Hodgkin’s lymphoma
The first analyses from two studies using PD-1 antibodies for the treatment of classical Hodgkin’s lymphoma will be reported. Investigators will report phase I results of nivolumab in 23 heavily pretreated patients with classical HL, and of pembrolizumab (MK-3475) in 15 patients with classical HL with previously failed treatment using brentuximab vedotin.
Preventing recurrence of Hodgkin’s lymphoma
Highly anticipated results from the Aethera trial, a phase III study of brentuximab vedotin in 327 patients at risk of progression following autologous stem cell transplant for Hodgkin’s lymphoma, will also be reported.
On Twitter@nikolaideslaura
Longer follow-up results on CAR-T therapy and early results from a novel BiTE therapy for patients with acute lymphoblastic leukemia, early results on checkpoint inhibitors to treat Hodgkin’s lymphoma, and phase III results on brentuximab vedotin to prevent recurrence of Hodgkin’s lymphoma will head up our onsite coverage of the American Society of Hematology Annual Meeting, to be held Dec. 6-9 in San Francisco.
Engineered T cells for treating patients with acute lymphoblastic leukemia
Reports on targeted therapies at ASH 2014 will include the latest follow-up of children with refractory acute lymphoblastic leukemia (ALL) who were treated with T-cells engineered with a chimeric antigen receptor targeting CD19, and results from a phase II study of blinatumomab, a bispecific T cell engager (BiTE) antibody construct, in patients with minimal residual disease B-precursor ALL.
Checkpoint inhibitors for treating patients with Hodgkin’s lymphoma
The first analyses from two studies using PD-1 antibodies for the treatment of classical Hodgkin’s lymphoma will be reported. Investigators will report phase I results of nivolumab in 23 heavily pretreated patients with classical HL, and of pembrolizumab (MK-3475) in 15 patients with classical HL with previously failed treatment using brentuximab vedotin.
Preventing recurrence of Hodgkin’s lymphoma
Highly anticipated results from the Aethera trial, a phase III study of brentuximab vedotin in 327 patients at risk of progression following autologous stem cell transplant for Hodgkin’s lymphoma, will also be reported.
On Twitter@nikolaideslaura
Has advertising for prostate cancer treatment gone too far?
Dr. Benjamin Davies has responded to advertising claims that recently ran in the Sunday New York Times Magazine and the New Yorker with an article in Forbes entitled “Prostate Cancer Advertising: Lies And The Damn Lies (Part 1).”
“I have a rating system for prostate cancer advertisements based on two self-evident tenets. First, cancer advertising should be scrupulously true and evidence based. Second, cancer patients are uniquely vulnerable to “hopeful” advertising (or “hopeium”) since often they face devastating odds of survival. We should all – collectively – shun advertisers that take advantage of these patients,” he wrote in the first of several articles. “I have no gripe with advertising your cancer care – just be horribly honest.”
Dr. Davies is associate professor of urology and director of the urologic oncology fellowship at the University of Pittsburgh. You can see the advertisements and read his articles here.
On Twitter @nikolaideslaura
Dr. Benjamin Davies has responded to advertising claims that recently ran in the Sunday New York Times Magazine and the New Yorker with an article in Forbes entitled “Prostate Cancer Advertising: Lies And The Damn Lies (Part 1).”
“I have a rating system for prostate cancer advertisements based on two self-evident tenets. First, cancer advertising should be scrupulously true and evidence based. Second, cancer patients are uniquely vulnerable to “hopeful” advertising (or “hopeium”) since often they face devastating odds of survival. We should all – collectively – shun advertisers that take advantage of these patients,” he wrote in the first of several articles. “I have no gripe with advertising your cancer care – just be horribly honest.”
Dr. Davies is associate professor of urology and director of the urologic oncology fellowship at the University of Pittsburgh. You can see the advertisements and read his articles here.
On Twitter @nikolaideslaura
Dr. Benjamin Davies has responded to advertising claims that recently ran in the Sunday New York Times Magazine and the New Yorker with an article in Forbes entitled “Prostate Cancer Advertising: Lies And The Damn Lies (Part 1).”
“I have a rating system for prostate cancer advertisements based on two self-evident tenets. First, cancer advertising should be scrupulously true and evidence based. Second, cancer patients are uniquely vulnerable to “hopeful” advertising (or “hopeium”) since often they face devastating odds of survival. We should all – collectively – shun advertisers that take advantage of these patients,” he wrote in the first of several articles. “I have no gripe with advertising your cancer care – just be horribly honest.”
Dr. Davies is associate professor of urology and director of the urologic oncology fellowship at the University of Pittsburgh. You can see the advertisements and read his articles here.
On Twitter @nikolaideslaura
FDA expands approval of ramucirumab for advanced gastric cancer
The Food and Drug Administration has approved the use of ramucirumab, a human vascular endothelial growth factor receptor 2 antagonist, in combination with paclitaxel as a treatment for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy, according to a letter from the FDA to the company. This follows the April approval of ramucirumab as a single agent for these patients.
Ramucirumab, which was granted orphan drug status, had been granted a priority review and is being marketed as Cyramza by Eli Lilly.
Ramucirumab is the only FDA-approved second-line treatment option for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose disease has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy, according to a company press release announcing the expanded approval.
This approval is based on the phase III RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma) trial, which randomized 665 patients to receive ramucirumamb plus paclitaxel or placebo plus paclitaxel.
Adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the annual Gastrointestinal Cancers Symposium in January.
The prescribing information for ramucirumab contains a boxed warning about the increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events.
On Twitter @nikolaideslaura
The Food and Drug Administration has approved the use of ramucirumab, a human vascular endothelial growth factor receptor 2 antagonist, in combination with paclitaxel as a treatment for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy, according to a letter from the FDA to the company. This follows the April approval of ramucirumab as a single agent for these patients.
Ramucirumab, which was granted orphan drug status, had been granted a priority review and is being marketed as Cyramza by Eli Lilly.
Ramucirumab is the only FDA-approved second-line treatment option for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose disease has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy, according to a company press release announcing the expanded approval.
This approval is based on the phase III RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma) trial, which randomized 665 patients to receive ramucirumamb plus paclitaxel or placebo plus paclitaxel.
Adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the annual Gastrointestinal Cancers Symposium in January.
The prescribing information for ramucirumab contains a boxed warning about the increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events.
On Twitter @nikolaideslaura
The Food and Drug Administration has approved the use of ramucirumab, a human vascular endothelial growth factor receptor 2 antagonist, in combination with paclitaxel as a treatment for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy, according to a letter from the FDA to the company. This follows the April approval of ramucirumab as a single agent for these patients.
Ramucirumab, which was granted orphan drug status, had been granted a priority review and is being marketed as Cyramza by Eli Lilly.
Ramucirumab is the only FDA-approved second-line treatment option for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose disease has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy, according to a company press release announcing the expanded approval.
This approval is based on the phase III RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma) trial, which randomized 665 patients to receive ramucirumamb plus paclitaxel or placebo plus paclitaxel.
Adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the annual Gastrointestinal Cancers Symposium in January.
The prescribing information for ramucirumab contains a boxed warning about the increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events.
On Twitter @nikolaideslaura
FDA approves new antiemetic drug combo
The Food and Drug Administration has approved an oral combination of two drugs for the prevention of nausea and vomiting in patients undergoing cancer chemotherapy.
The combination of palonosetron, approved in 2008, and a new drug, netupitant, prevent nausea and vomiting during both the acute phase and delayed phase (from 25 to 120 hours) after the start of chemotherapy, according to an FDA press statement. The effectiveness of the combination drug, marketed as Akynzeo by Eisai, was established in two clinical trials of 1,720 participants receiving cancer chemotherapy. Participants were randomly assigned to receive Akynzeo or oral palonosetron, the FDA statement said.
In the first trial, 98.5%, 90.4%, and 89.6% of Akynzeo-treated participants did not experience any vomiting or require rescue medication for nausea during the acute, delayed, and overall phases, respectively, compared with 89.7%, 80.1%, and 76.5% of participants treated with oral palonosetron.
The second trial showed similar results.Common side effects of Akynzeo in the clinical trials were headache, asthenia, fatigue, dyspepsia, and constipation, the FDA noted in the statement.
The Food and Drug Administration has approved an oral combination of two drugs for the prevention of nausea and vomiting in patients undergoing cancer chemotherapy.
The combination of palonosetron, approved in 2008, and a new drug, netupitant, prevent nausea and vomiting during both the acute phase and delayed phase (from 25 to 120 hours) after the start of chemotherapy, according to an FDA press statement. The effectiveness of the combination drug, marketed as Akynzeo by Eisai, was established in two clinical trials of 1,720 participants receiving cancer chemotherapy. Participants were randomly assigned to receive Akynzeo or oral palonosetron, the FDA statement said.
In the first trial, 98.5%, 90.4%, and 89.6% of Akynzeo-treated participants did not experience any vomiting or require rescue medication for nausea during the acute, delayed, and overall phases, respectively, compared with 89.7%, 80.1%, and 76.5% of participants treated with oral palonosetron.
The second trial showed similar results.Common side effects of Akynzeo in the clinical trials were headache, asthenia, fatigue, dyspepsia, and constipation, the FDA noted in the statement.
The Food and Drug Administration has approved an oral combination of two drugs for the prevention of nausea and vomiting in patients undergoing cancer chemotherapy.
The combination of palonosetron, approved in 2008, and a new drug, netupitant, prevent nausea and vomiting during both the acute phase and delayed phase (from 25 to 120 hours) after the start of chemotherapy, according to an FDA press statement. The effectiveness of the combination drug, marketed as Akynzeo by Eisai, was established in two clinical trials of 1,720 participants receiving cancer chemotherapy. Participants were randomly assigned to receive Akynzeo or oral palonosetron, the FDA statement said.
In the first trial, 98.5%, 90.4%, and 89.6% of Akynzeo-treated participants did not experience any vomiting or require rescue medication for nausea during the acute, delayed, and overall phases, respectively, compared with 89.7%, 80.1%, and 76.5% of participants treated with oral palonosetron.
The second trial showed similar results.Common side effects of Akynzeo in the clinical trials were headache, asthenia, fatigue, dyspepsia, and constipation, the FDA noted in the statement.
Researchers deem tumor-infiltrating lymphocytes valid prognostic biomarker in TNBC
Evidence continues to accumulate that a breast cancer patient’s immune system plays a role in the outcome from aggressive disease. According to recently published studies, the presence of tumor-infiltrating lymphocytes present at the time of diagnosis provides a fairly consistent biomarker of prognosis for triple-negative breast cancer, and possibly for HER2-positive breast cancer, and furthermore, may predict treatment benefit for some patients.
In an analysis of tumor samples from 12,439 women diagnosed with breast cancer, enrolled in four studies, the presence of cytotoxic T cells within ER-negative tumors was associated with a 21%-28% reduction in the relative risk of dying of breast cancer, depending on the location of the T cells, Dr. Raza Ali and associates reported online in Annals of Oncology.
Just over one-fifth of the 12,439 patients died of breast cancer within 10 years of diagnosis; median survival was 9.57 years. Among those with ER-negative tumors, the presence of CD8-positive lymphocytes was independently associated with a reduced relative risk of death from breast cancer. The adjusted hazard ratio (HR) for the presence of CD8-positive lymphocytes within the tumor was 0.72 (95% confidence interval, 0.62-0.84; P = .00003) and, for lymphocytes within the stroma, the HR was 0.79 (95% CI, 0.67-0.93; P = .004), Dr. Ali of the Cancer Research U.K. Cambridge Institute, and associates reported (Ann. Oncol. 25:1536-43, 2014).
Overall, the presence of CD8-positive lymphocytes was not associated with breast cancer–specific survival in women with ER-positive breast tumors; however, in a subgroup analysis, the prognostic effect of lymphocytes within ER-positive tumors did differ by HER2 status (P [heterogeneity] = .006). The HR for lymphocytes within the ER-positive, HER2-positive tumors was 0.73 (95% CI, 0.56-0.96; P = .022) after adjustment for known prognostic factors.
Furthermore, there was evidence from the National Epirubicin Adjuvant Trial of greater benefit from anthracyclines in patients with CD8-positive tumors (HR = 0.60; 95% CI, 0.37-0.96) versus patients with CD8-negative tumors (HR = 1.47; 95% CI, 0.72-3.02; P [heterogeneity] = .039), Dr. Ali and associates said.
The investigators used immunochemistry to quantify both cytotoxic CD8-positive T cells, a potential biomarker for the tumor-associated immune response, and a protein, FOXP3, expressed on T-regulatory lymphocytes and a potential biomarker for an immunosuppressive tumor effect. They found no association between FOXP3 expression and breast cancer mortality, irrespective of ER status.
In another recent report, stromal lymphocyte infiltration was significantly correlated with distant recurrence and overall survival in patients with triple-negative breast cancer (TNBC). In the prospective-retrospective validation study, two blinded pathologists evaluated 506 randomly selected tumor samples from two prospective Eastern Cooperative Oncology Group adjuvant phase III clinical trials, Dr. Sylvia Adams and associates reported online in the Journal of Clinical Oncology.
Investigators looked for both intraepithelial tumor-infiltrating lymphocytes (TILs), defined as the percentage of lymphocytes in direct contact with the tumor cells, and stromal TILs, defined as the percentage of tumor stroma containing infiltrating lymphocytes. The majority of 481 evaluable cancers had lymphocyte infiltration, which was significantly more likely to be found in the stroma (80% had at least 10% stromal TILs) than in the intraepithelial area (15% had at least 10% intraepithelial TILs), Dr. Adams of New York University, New York, and associates reported.
After a median follow-up of 10.6 years, 107 events of distant recurrence and 142 deaths were reported. Investigators found higher stromal TIL scores were associated with a better prognosis; each 10-point increase in the stromal TIL score was associated with an 18% decrease in the risk of distant recurrence, and a 19% decrease in the risk of death (distant recurrence-free interval HR, 0.82; 95% CI, 0.68-0.99; P = .04; and overall survival HR, 0.81; 95% CI, 0.69-0.95; P =.01) the investigators reported (J. Clin. Onc. 2014 [doi:10.1200/JCO.2013.55.0491]).
The intraepithelial score correlated with both distant recurrence-free interval (DRFI) and overall survival (OS) but did not reach significance (DRFI: HR, 0.53; 95% CI, 0.25-1.09; P = .08; OS: HR, 0.64; 95% CI, 0.39-1.05; P = .08). Multivariable analysis confirmed stromal TILs to be an independent prognostic marker of DRFI and OS, the authors reported.
These accumulating data are prompting researchers to speculate on the addition of immune checkpoint inhibitors to breast cancer treatment regimens. In an editorial accompanying Dr. Adams’s report, Dr. Sherene Loi of the Peter MacCallum Cancer Centre, East Melbourne, Australia, wrote: "Given the correlation of programmed death ligand 1 (PD-L1 or CD274) with the presence of TILs, the most tantalizing question is whether current T-cell checkpoint inhibitors, such as anti–PD-1 (programmed cell death 1) antibodies, will be helpful in the treatment of TNBC, a subtype of breast cancer that is sorely in need of more effective therapies"(J. Clin. Onc. 2014 [doi:10.1200/JCO.2014.56.7677]).
In a separate report published recently, Dr. Loi and associates also found a consistent prognostic association between tumor-infiltrating lymphocytes and TNBC. In addition, these investigators found a statistically significant interaction between TILs as a continuous variable and trastuzumab treatment, according to the report published online in Annals of Oncology.
For the study, two pathologists independently quantified stromal TILs in 935 available tumor samples from the FinHER adjuvant trial, a phase III trial that enrolled 1,010 early-stage breast cancer patients, including 232 with HER2-positive disease. The primary endpoint of distant disease-free survival and interactions with trastuzumab were studied in Cox regression models.
Dr. Loi and associates found a significant association between TILs and a good prognosis in TNBC but not in luminal or HER2-positive subtypes. In patients with TNBC, each 10% increase in TILs was associated with a 13% reduction in the relative risk of distant recurrence (adjusted for clinicopathologic factors HR, 0.77; 95% CI, 0.61-0.98; P =.02). There was no statistical significance observed for OS, probably because of the small number of events observed, the investigators suggested (Ann. Onc. 2014;25:1544-50).
The investigators also found a statistically significant interaction between TILs as a continuous variable and trastuzumab treatment (P interaction DDFS, P = .025; P interaction OS, P = .08). For the primary endpoint of DDFS, each 10% increment in lymphocytic infiltrate was associated with an 18% reduction in the relative risk of distant recurrence in patients who received trastuzumab in addition to their chemotherapy, Dr. Loi and associates reported.
The investigators concluded that the evidence is now sufficient to consider TILs a valid prognostic biomarker in TNBC. "The use of a second clinical trial data set to confirm this finding, in addition to further data presented recently in abstract form, suggest that the evidence base for the clinical validity of TILs as a prognostic biomarker in TNBC could now be considered level I," they said.
Furthermore, the level of TILs present at diagnosis in women with HER2-positive disease may also prove to be a useful biomarker, and the investigators suggested their data indicate checkpoint inhibitors could be useful for both TNBC and HER2-positive disease. "Our data strongly support the clinical relevance of antitumor immunity in these two breast cancer subtypes. Further studies will be required to determine how trastuzumab alters the immune microenvironment and if the addition of an immune checkpoint inhibitor can further improve clinical outcomes in these two breast cancer subtypes," Dr. Loi and associates wrote.
Dr. Ali’s study was supported by Cancer Research U.K. and the NIHR Cambridge Biomedical Research Centre. One coauthor reported receiving consultancy fees from Bioclassifier amounting to less than $10,000 and not bearing directly on the study. All other authors declared no conflicts of interest. Dr. Ali and associates reported no potential conflicts of interest.
Dr. Adams’s study was supported by grants from the U.S. National Cancer Institute, U.S. Department of Health and Human Services, Sanofi-Aventis, and the Breast Cancer Research Foundation, and by a Komen Scholar Award.
Dr. Loi’s study was funded by the European Union Framework 7 program, the RESPONSIFY project, and the Breast Cancer Research Foundation. Dr. Loi and associates declared no conflicts of interest.
On Twitter @nikolaideslaura
For decades, pathologists have noted that most human tumors are infiltrated by lymphocytes. The clinical significance of tumor-infiltrating lymphocytes (TILs) came into focus over the past decade, with large studies of sufficient size to detect statistically significant correlations with survival. The strongest evidence for tumor infiltration by T cells and favorable clinical outcome has been established in colorectal carcinoma. Similar correlations have now been observed in essentially all tumor types, including melanoma, head and neck cancer, lung cancer, and others. Over the past year, three large studies have firmly established the clinical significance of TILs in breast cancer. The largest study followed clinical outcomes of 12,439 newly diagnosed breast cancer patients in the United Kingdom and Canada over the course of 10 years. The study showed a survival benefit of CD8-positive T cells within breast tumors in both triple-negative and ER-negative/HER2-positive patients. A survival benefit from CD8-positive T cells within triple-negative breast tumors was also shown in two additional studies: ECOG and FinHER studies representing an additional 1,491 patients analyzed.
Together, these studies firmly established the prognostic significance of tumor-infiltrating CD8-positive T cells in triple-negative and HER2-positive breast cancer. Furthermore, these studies also found that tumor-infiltrating CD8-positive T cells are predictive of clinical benefit from trastuzumab and anthracyclines. Thus, the presence of intratumoral CD8-positive T cells can help guide breast cancer patient management and should be included in routine pathologic examinations – a concept the authors called "immunoscore."
However, T cells are often exhausted and dysfunctional within the tumor microenvironment. Recent studies have shown that tumor-infiltrating T cells express several immune checkpoint molecules – including CTLA-4, PD-1, TIM-3, and LAG-3 – which when engaged with their counterligands (B7 and PDL-1, for example) – leads to inhibition of T-cell function. This spawned the development of antibodies to block immune checkpoint molecules, which have demonstrated exciting clinical efficacy. An anti–CTLA-4 antibody (ipilimumab, Yervoy) demonstrated efficacy in phase III clinical trials and was approved by the U.S. Food and Drug Administration for metastatic melanoma in 2011. Antibodies blocking PD-1, or its counterligand PD-L1, are under clinical development by at least seven companies. Phase II data show encouraging clinical responses and potentially less toxicities than anti–CTLA-4. Importantly, these immune checkpoint inhibitors led to survival curves that plateau at 15%-25%, raising the exciting possibility that some patients may be cured – by agents that act on the host immune system only. These results further strengthen the notion that the host immune system can respond to cancer, that the success of the endogenous antitumor immune response determines clinical outcome and response to even conventional therapies, and that this immune response can be further enhanced for clinical benefit.
Other immune cell types also infiltrate human tumors, including B, NK, and myeloid cells. The balance of these different immune cell populations within tumors – and tumor-draining lymph nodes (TDLNs) – likely drives clinical outcome. Future studies need to account for this additional complexity, which will be possible using novel flow cytometry and image analysis approaches. A deeper understanding of the interplay between different immune cell populations within tumors and TDLNs will uncover ways to enhance the total effect of cancer immunotherapies, including checkpoint inhibitors and adoptive T-cell therapy.
Dr. Peter P. Lee is Billy Wilder Endowed Professor and Chair, department of cancer immunotherapeutics and tumor immunology at the City of Hope Comprehensive Cancer Center, Duarte, Calif. Dr. Lee said he had no relevant financial conflicts.
For decades, pathologists have noted that most human tumors are infiltrated by lymphocytes. The clinical significance of tumor-infiltrating lymphocytes (TILs) came into focus over the past decade, with large studies of sufficient size to detect statistically significant correlations with survival. The strongest evidence for tumor infiltration by T cells and favorable clinical outcome has been established in colorectal carcinoma. Similar correlations have now been observed in essentially all tumor types, including melanoma, head and neck cancer, lung cancer, and others. Over the past year, three large studies have firmly established the clinical significance of TILs in breast cancer. The largest study followed clinical outcomes of 12,439 newly diagnosed breast cancer patients in the United Kingdom and Canada over the course of 10 years. The study showed a survival benefit of CD8-positive T cells within breast tumors in both triple-negative and ER-negative/HER2-positive patients. A survival benefit from CD8-positive T cells within triple-negative breast tumors was also shown in two additional studies: ECOG and FinHER studies representing an additional 1,491 patients analyzed.
Together, these studies firmly established the prognostic significance of tumor-infiltrating CD8-positive T cells in triple-negative and HER2-positive breast cancer. Furthermore, these studies also found that tumor-infiltrating CD8-positive T cells are predictive of clinical benefit from trastuzumab and anthracyclines. Thus, the presence of intratumoral CD8-positive T cells can help guide breast cancer patient management and should be included in routine pathologic examinations – a concept the authors called "immunoscore."
However, T cells are often exhausted and dysfunctional within the tumor microenvironment. Recent studies have shown that tumor-infiltrating T cells express several immune checkpoint molecules – including CTLA-4, PD-1, TIM-3, and LAG-3 – which when engaged with their counterligands (B7 and PDL-1, for example) – leads to inhibition of T-cell function. This spawned the development of antibodies to block immune checkpoint molecules, which have demonstrated exciting clinical efficacy. An anti–CTLA-4 antibody (ipilimumab, Yervoy) demonstrated efficacy in phase III clinical trials and was approved by the U.S. Food and Drug Administration for metastatic melanoma in 2011. Antibodies blocking PD-1, or its counterligand PD-L1, are under clinical development by at least seven companies. Phase II data show encouraging clinical responses and potentially less toxicities than anti–CTLA-4. Importantly, these immune checkpoint inhibitors led to survival curves that plateau at 15%-25%, raising the exciting possibility that some patients may be cured – by agents that act on the host immune system only. These results further strengthen the notion that the host immune system can respond to cancer, that the success of the endogenous antitumor immune response determines clinical outcome and response to even conventional therapies, and that this immune response can be further enhanced for clinical benefit.
Other immune cell types also infiltrate human tumors, including B, NK, and myeloid cells. The balance of these different immune cell populations within tumors – and tumor-draining lymph nodes (TDLNs) – likely drives clinical outcome. Future studies need to account for this additional complexity, which will be possible using novel flow cytometry and image analysis approaches. A deeper understanding of the interplay between different immune cell populations within tumors and TDLNs will uncover ways to enhance the total effect of cancer immunotherapies, including checkpoint inhibitors and adoptive T-cell therapy.
Dr. Peter P. Lee is Billy Wilder Endowed Professor and Chair, department of cancer immunotherapeutics and tumor immunology at the City of Hope Comprehensive Cancer Center, Duarte, Calif. Dr. Lee said he had no relevant financial conflicts.
For decades, pathologists have noted that most human tumors are infiltrated by lymphocytes. The clinical significance of tumor-infiltrating lymphocytes (TILs) came into focus over the past decade, with large studies of sufficient size to detect statistically significant correlations with survival. The strongest evidence for tumor infiltration by T cells and favorable clinical outcome has been established in colorectal carcinoma. Similar correlations have now been observed in essentially all tumor types, including melanoma, head and neck cancer, lung cancer, and others. Over the past year, three large studies have firmly established the clinical significance of TILs in breast cancer. The largest study followed clinical outcomes of 12,439 newly diagnosed breast cancer patients in the United Kingdom and Canada over the course of 10 years. The study showed a survival benefit of CD8-positive T cells within breast tumors in both triple-negative and ER-negative/HER2-positive patients. A survival benefit from CD8-positive T cells within triple-negative breast tumors was also shown in two additional studies: ECOG and FinHER studies representing an additional 1,491 patients analyzed.
Together, these studies firmly established the prognostic significance of tumor-infiltrating CD8-positive T cells in triple-negative and HER2-positive breast cancer. Furthermore, these studies also found that tumor-infiltrating CD8-positive T cells are predictive of clinical benefit from trastuzumab and anthracyclines. Thus, the presence of intratumoral CD8-positive T cells can help guide breast cancer patient management and should be included in routine pathologic examinations – a concept the authors called "immunoscore."
However, T cells are often exhausted and dysfunctional within the tumor microenvironment. Recent studies have shown that tumor-infiltrating T cells express several immune checkpoint molecules – including CTLA-4, PD-1, TIM-3, and LAG-3 – which when engaged with their counterligands (B7 and PDL-1, for example) – leads to inhibition of T-cell function. This spawned the development of antibodies to block immune checkpoint molecules, which have demonstrated exciting clinical efficacy. An anti–CTLA-4 antibody (ipilimumab, Yervoy) demonstrated efficacy in phase III clinical trials and was approved by the U.S. Food and Drug Administration for metastatic melanoma in 2011. Antibodies blocking PD-1, or its counterligand PD-L1, are under clinical development by at least seven companies. Phase II data show encouraging clinical responses and potentially less toxicities than anti–CTLA-4. Importantly, these immune checkpoint inhibitors led to survival curves that plateau at 15%-25%, raising the exciting possibility that some patients may be cured – by agents that act on the host immune system only. These results further strengthen the notion that the host immune system can respond to cancer, that the success of the endogenous antitumor immune response determines clinical outcome and response to even conventional therapies, and that this immune response can be further enhanced for clinical benefit.
Other immune cell types also infiltrate human tumors, including B, NK, and myeloid cells. The balance of these different immune cell populations within tumors – and tumor-draining lymph nodes (TDLNs) – likely drives clinical outcome. Future studies need to account for this additional complexity, which will be possible using novel flow cytometry and image analysis approaches. A deeper understanding of the interplay between different immune cell populations within tumors and TDLNs will uncover ways to enhance the total effect of cancer immunotherapies, including checkpoint inhibitors and adoptive T-cell therapy.
Dr. Peter P. Lee is Billy Wilder Endowed Professor and Chair, department of cancer immunotherapeutics and tumor immunology at the City of Hope Comprehensive Cancer Center, Duarte, Calif. Dr. Lee said he had no relevant financial conflicts.
Evidence continues to accumulate that a breast cancer patient’s immune system plays a role in the outcome from aggressive disease. According to recently published studies, the presence of tumor-infiltrating lymphocytes present at the time of diagnosis provides a fairly consistent biomarker of prognosis for triple-negative breast cancer, and possibly for HER2-positive breast cancer, and furthermore, may predict treatment benefit for some patients.
In an analysis of tumor samples from 12,439 women diagnosed with breast cancer, enrolled in four studies, the presence of cytotoxic T cells within ER-negative tumors was associated with a 21%-28% reduction in the relative risk of dying of breast cancer, depending on the location of the T cells, Dr. Raza Ali and associates reported online in Annals of Oncology.
Just over one-fifth of the 12,439 patients died of breast cancer within 10 years of diagnosis; median survival was 9.57 years. Among those with ER-negative tumors, the presence of CD8-positive lymphocytes was independently associated with a reduced relative risk of death from breast cancer. The adjusted hazard ratio (HR) for the presence of CD8-positive lymphocytes within the tumor was 0.72 (95% confidence interval, 0.62-0.84; P = .00003) and, for lymphocytes within the stroma, the HR was 0.79 (95% CI, 0.67-0.93; P = .004), Dr. Ali of the Cancer Research U.K. Cambridge Institute, and associates reported (Ann. Oncol. 25:1536-43, 2014).
Overall, the presence of CD8-positive lymphocytes was not associated with breast cancer–specific survival in women with ER-positive breast tumors; however, in a subgroup analysis, the prognostic effect of lymphocytes within ER-positive tumors did differ by HER2 status (P [heterogeneity] = .006). The HR for lymphocytes within the ER-positive, HER2-positive tumors was 0.73 (95% CI, 0.56-0.96; P = .022) after adjustment for known prognostic factors.
Furthermore, there was evidence from the National Epirubicin Adjuvant Trial of greater benefit from anthracyclines in patients with CD8-positive tumors (HR = 0.60; 95% CI, 0.37-0.96) versus patients with CD8-negative tumors (HR = 1.47; 95% CI, 0.72-3.02; P [heterogeneity] = .039), Dr. Ali and associates said.
The investigators used immunochemistry to quantify both cytotoxic CD8-positive T cells, a potential biomarker for the tumor-associated immune response, and a protein, FOXP3, expressed on T-regulatory lymphocytes and a potential biomarker for an immunosuppressive tumor effect. They found no association between FOXP3 expression and breast cancer mortality, irrespective of ER status.
In another recent report, stromal lymphocyte infiltration was significantly correlated with distant recurrence and overall survival in patients with triple-negative breast cancer (TNBC). In the prospective-retrospective validation study, two blinded pathologists evaluated 506 randomly selected tumor samples from two prospective Eastern Cooperative Oncology Group adjuvant phase III clinical trials, Dr. Sylvia Adams and associates reported online in the Journal of Clinical Oncology.
Investigators looked for both intraepithelial tumor-infiltrating lymphocytes (TILs), defined as the percentage of lymphocytes in direct contact with the tumor cells, and stromal TILs, defined as the percentage of tumor stroma containing infiltrating lymphocytes. The majority of 481 evaluable cancers had lymphocyte infiltration, which was significantly more likely to be found in the stroma (80% had at least 10% stromal TILs) than in the intraepithelial area (15% had at least 10% intraepithelial TILs), Dr. Adams of New York University, New York, and associates reported.
After a median follow-up of 10.6 years, 107 events of distant recurrence and 142 deaths were reported. Investigators found higher stromal TIL scores were associated with a better prognosis; each 10-point increase in the stromal TIL score was associated with an 18% decrease in the risk of distant recurrence, and a 19% decrease in the risk of death (distant recurrence-free interval HR, 0.82; 95% CI, 0.68-0.99; P = .04; and overall survival HR, 0.81; 95% CI, 0.69-0.95; P =.01) the investigators reported (J. Clin. Onc. 2014 [doi:10.1200/JCO.2013.55.0491]).
The intraepithelial score correlated with both distant recurrence-free interval (DRFI) and overall survival (OS) but did not reach significance (DRFI: HR, 0.53; 95% CI, 0.25-1.09; P = .08; OS: HR, 0.64; 95% CI, 0.39-1.05; P = .08). Multivariable analysis confirmed stromal TILs to be an independent prognostic marker of DRFI and OS, the authors reported.
These accumulating data are prompting researchers to speculate on the addition of immune checkpoint inhibitors to breast cancer treatment regimens. In an editorial accompanying Dr. Adams’s report, Dr. Sherene Loi of the Peter MacCallum Cancer Centre, East Melbourne, Australia, wrote: "Given the correlation of programmed death ligand 1 (PD-L1 or CD274) with the presence of TILs, the most tantalizing question is whether current T-cell checkpoint inhibitors, such as anti–PD-1 (programmed cell death 1) antibodies, will be helpful in the treatment of TNBC, a subtype of breast cancer that is sorely in need of more effective therapies"(J. Clin. Onc. 2014 [doi:10.1200/JCO.2014.56.7677]).
In a separate report published recently, Dr. Loi and associates also found a consistent prognostic association between tumor-infiltrating lymphocytes and TNBC. In addition, these investigators found a statistically significant interaction between TILs as a continuous variable and trastuzumab treatment, according to the report published online in Annals of Oncology.
For the study, two pathologists independently quantified stromal TILs in 935 available tumor samples from the FinHER adjuvant trial, a phase III trial that enrolled 1,010 early-stage breast cancer patients, including 232 with HER2-positive disease. The primary endpoint of distant disease-free survival and interactions with trastuzumab were studied in Cox regression models.
Dr. Loi and associates found a significant association between TILs and a good prognosis in TNBC but not in luminal or HER2-positive subtypes. In patients with TNBC, each 10% increase in TILs was associated with a 13% reduction in the relative risk of distant recurrence (adjusted for clinicopathologic factors HR, 0.77; 95% CI, 0.61-0.98; P =.02). There was no statistical significance observed for OS, probably because of the small number of events observed, the investigators suggested (Ann. Onc. 2014;25:1544-50).
The investigators also found a statistically significant interaction between TILs as a continuous variable and trastuzumab treatment (P interaction DDFS, P = .025; P interaction OS, P = .08). For the primary endpoint of DDFS, each 10% increment in lymphocytic infiltrate was associated with an 18% reduction in the relative risk of distant recurrence in patients who received trastuzumab in addition to their chemotherapy, Dr. Loi and associates reported.
The investigators concluded that the evidence is now sufficient to consider TILs a valid prognostic biomarker in TNBC. "The use of a second clinical trial data set to confirm this finding, in addition to further data presented recently in abstract form, suggest that the evidence base for the clinical validity of TILs as a prognostic biomarker in TNBC could now be considered level I," they said.
Furthermore, the level of TILs present at diagnosis in women with HER2-positive disease may also prove to be a useful biomarker, and the investigators suggested their data indicate checkpoint inhibitors could be useful for both TNBC and HER2-positive disease. "Our data strongly support the clinical relevance of antitumor immunity in these two breast cancer subtypes. Further studies will be required to determine how trastuzumab alters the immune microenvironment and if the addition of an immune checkpoint inhibitor can further improve clinical outcomes in these two breast cancer subtypes," Dr. Loi and associates wrote.
Dr. Ali’s study was supported by Cancer Research U.K. and the NIHR Cambridge Biomedical Research Centre. One coauthor reported receiving consultancy fees from Bioclassifier amounting to less than $10,000 and not bearing directly on the study. All other authors declared no conflicts of interest. Dr. Ali and associates reported no potential conflicts of interest.
Dr. Adams’s study was supported by grants from the U.S. National Cancer Institute, U.S. Department of Health and Human Services, Sanofi-Aventis, and the Breast Cancer Research Foundation, and by a Komen Scholar Award.
Dr. Loi’s study was funded by the European Union Framework 7 program, the RESPONSIFY project, and the Breast Cancer Research Foundation. Dr. Loi and associates declared no conflicts of interest.
On Twitter @nikolaideslaura
Evidence continues to accumulate that a breast cancer patient’s immune system plays a role in the outcome from aggressive disease. According to recently published studies, the presence of tumor-infiltrating lymphocytes present at the time of diagnosis provides a fairly consistent biomarker of prognosis for triple-negative breast cancer, and possibly for HER2-positive breast cancer, and furthermore, may predict treatment benefit for some patients.
In an analysis of tumor samples from 12,439 women diagnosed with breast cancer, enrolled in four studies, the presence of cytotoxic T cells within ER-negative tumors was associated with a 21%-28% reduction in the relative risk of dying of breast cancer, depending on the location of the T cells, Dr. Raza Ali and associates reported online in Annals of Oncology.
Just over one-fifth of the 12,439 patients died of breast cancer within 10 years of diagnosis; median survival was 9.57 years. Among those with ER-negative tumors, the presence of CD8-positive lymphocytes was independently associated with a reduced relative risk of death from breast cancer. The adjusted hazard ratio (HR) for the presence of CD8-positive lymphocytes within the tumor was 0.72 (95% confidence interval, 0.62-0.84; P = .00003) and, for lymphocytes within the stroma, the HR was 0.79 (95% CI, 0.67-0.93; P = .004), Dr. Ali of the Cancer Research U.K. Cambridge Institute, and associates reported (Ann. Oncol. 25:1536-43, 2014).
Overall, the presence of CD8-positive lymphocytes was not associated with breast cancer–specific survival in women with ER-positive breast tumors; however, in a subgroup analysis, the prognostic effect of lymphocytes within ER-positive tumors did differ by HER2 status (P [heterogeneity] = .006). The HR for lymphocytes within the ER-positive, HER2-positive tumors was 0.73 (95% CI, 0.56-0.96; P = .022) after adjustment for known prognostic factors.
Furthermore, there was evidence from the National Epirubicin Adjuvant Trial of greater benefit from anthracyclines in patients with CD8-positive tumors (HR = 0.60; 95% CI, 0.37-0.96) versus patients with CD8-negative tumors (HR = 1.47; 95% CI, 0.72-3.02; P [heterogeneity] = .039), Dr. Ali and associates said.
The investigators used immunochemistry to quantify both cytotoxic CD8-positive T cells, a potential biomarker for the tumor-associated immune response, and a protein, FOXP3, expressed on T-regulatory lymphocytes and a potential biomarker for an immunosuppressive tumor effect. They found no association between FOXP3 expression and breast cancer mortality, irrespective of ER status.
In another recent report, stromal lymphocyte infiltration was significantly correlated with distant recurrence and overall survival in patients with triple-negative breast cancer (TNBC). In the prospective-retrospective validation study, two blinded pathologists evaluated 506 randomly selected tumor samples from two prospective Eastern Cooperative Oncology Group adjuvant phase III clinical trials, Dr. Sylvia Adams and associates reported online in the Journal of Clinical Oncology.
Investigators looked for both intraepithelial tumor-infiltrating lymphocytes (TILs), defined as the percentage of lymphocytes in direct contact with the tumor cells, and stromal TILs, defined as the percentage of tumor stroma containing infiltrating lymphocytes. The majority of 481 evaluable cancers had lymphocyte infiltration, which was significantly more likely to be found in the stroma (80% had at least 10% stromal TILs) than in the intraepithelial area (15% had at least 10% intraepithelial TILs), Dr. Adams of New York University, New York, and associates reported.
After a median follow-up of 10.6 years, 107 events of distant recurrence and 142 deaths were reported. Investigators found higher stromal TIL scores were associated with a better prognosis; each 10-point increase in the stromal TIL score was associated with an 18% decrease in the risk of distant recurrence, and a 19% decrease in the risk of death (distant recurrence-free interval HR, 0.82; 95% CI, 0.68-0.99; P = .04; and overall survival HR, 0.81; 95% CI, 0.69-0.95; P =.01) the investigators reported (J. Clin. Onc. 2014 [doi:10.1200/JCO.2013.55.0491]).
The intraepithelial score correlated with both distant recurrence-free interval (DRFI) and overall survival (OS) but did not reach significance (DRFI: HR, 0.53; 95% CI, 0.25-1.09; P = .08; OS: HR, 0.64; 95% CI, 0.39-1.05; P = .08). Multivariable analysis confirmed stromal TILs to be an independent prognostic marker of DRFI and OS, the authors reported.
These accumulating data are prompting researchers to speculate on the addition of immune checkpoint inhibitors to breast cancer treatment regimens. In an editorial accompanying Dr. Adams’s report, Dr. Sherene Loi of the Peter MacCallum Cancer Centre, East Melbourne, Australia, wrote: "Given the correlation of programmed death ligand 1 (PD-L1 or CD274) with the presence of TILs, the most tantalizing question is whether current T-cell checkpoint inhibitors, such as anti–PD-1 (programmed cell death 1) antibodies, will be helpful in the treatment of TNBC, a subtype of breast cancer that is sorely in need of more effective therapies"(J. Clin. Onc. 2014 [doi:10.1200/JCO.2014.56.7677]).
In a separate report published recently, Dr. Loi and associates also found a consistent prognostic association between tumor-infiltrating lymphocytes and TNBC. In addition, these investigators found a statistically significant interaction between TILs as a continuous variable and trastuzumab treatment, according to the report published online in Annals of Oncology.
For the study, two pathologists independently quantified stromal TILs in 935 available tumor samples from the FinHER adjuvant trial, a phase III trial that enrolled 1,010 early-stage breast cancer patients, including 232 with HER2-positive disease. The primary endpoint of distant disease-free survival and interactions with trastuzumab were studied in Cox regression models.
Dr. Loi and associates found a significant association between TILs and a good prognosis in TNBC but not in luminal or HER2-positive subtypes. In patients with TNBC, each 10% increase in TILs was associated with a 13% reduction in the relative risk of distant recurrence (adjusted for clinicopathologic factors HR, 0.77; 95% CI, 0.61-0.98; P =.02). There was no statistical significance observed for OS, probably because of the small number of events observed, the investigators suggested (Ann. Onc. 2014;25:1544-50).
The investigators also found a statistically significant interaction between TILs as a continuous variable and trastuzumab treatment (P interaction DDFS, P = .025; P interaction OS, P = .08). For the primary endpoint of DDFS, each 10% increment in lymphocytic infiltrate was associated with an 18% reduction in the relative risk of distant recurrence in patients who received trastuzumab in addition to their chemotherapy, Dr. Loi and associates reported.
The investigators concluded that the evidence is now sufficient to consider TILs a valid prognostic biomarker in TNBC. "The use of a second clinical trial data set to confirm this finding, in addition to further data presented recently in abstract form, suggest that the evidence base for the clinical validity of TILs as a prognostic biomarker in TNBC could now be considered level I," they said.
Furthermore, the level of TILs present at diagnosis in women with HER2-positive disease may also prove to be a useful biomarker, and the investigators suggested their data indicate checkpoint inhibitors could be useful for both TNBC and HER2-positive disease. "Our data strongly support the clinical relevance of antitumor immunity in these two breast cancer subtypes. Further studies will be required to determine how trastuzumab alters the immune microenvironment and if the addition of an immune checkpoint inhibitor can further improve clinical outcomes in these two breast cancer subtypes," Dr. Loi and associates wrote.
Dr. Ali’s study was supported by Cancer Research U.K. and the NIHR Cambridge Biomedical Research Centre. One coauthor reported receiving consultancy fees from Bioclassifier amounting to less than $10,000 and not bearing directly on the study. All other authors declared no conflicts of interest. Dr. Ali and associates reported no potential conflicts of interest.
Dr. Adams’s study was supported by grants from the U.S. National Cancer Institute, U.S. Department of Health and Human Services, Sanofi-Aventis, and the Breast Cancer Research Foundation, and by a Komen Scholar Award.
Dr. Loi’s study was funded by the European Union Framework 7 program, the RESPONSIFY project, and the Breast Cancer Research Foundation. Dr. Loi and associates declared no conflicts of interest.
On Twitter @nikolaideslaura
FROM ANNALS OF ONCOLOGY AND JOURNAL OF CLINICAL ONCOLOGY
Lung-MAP trial launched, matching patients to treatments based on tumor profiles
A phase II/III trial using genomic profiling to match patients with investigational treatments is currently recruiting patients with advanced squamous cell lung cancer.
The Lung-MAP (Lung Cancer Master Protocol) trial is a public-private collaboration among the National Cancer Institute (NCI), SWOG Cancer Research, Friends of Cancer Research, the Foundation for the National Institutes of Health, Foundation Medicine, and five pharmaceutical companies (Amgen, Genentech, Pfizer, AstraZeneca, and AstraZeneca’s global biologics R&D arm, MedImmune).
"Lung-MAP represents the first of several planned large, genomically driven treatment trials that will be conducted by NCI’s newly formed National Clinical Trials Network (NCTN)," Dr. Jeffrey S. Abrams, associate director of NCI’s Cancer Therapy Evaluation Program, said in a press release announcing the trial launch. "The restructuring and consolidation of NCI’s large trial treatment program, resulting in the formation of the NCTN, is quite timely, as it now can offer an ideal platform for bringing the benefits of more precise molecular diagnostics to cancer patients in communities large and small, " he said.
Lung-MAP is expected to enroll 10,000 patients and be completed in 2022. To be eligible, patients will have progressed after receiving exactly one front-line, platinum-containing metastatic chemotherapy regimen. Between 500 and 1,000 patients will be screened per year for more than 200 cancer-related gene alterations. Based on the tumor profiles, all patients will then be assigned to one of five initial treatment arms, testing four investigational targeted treatments and an anti-PD-L1 immunotherapy.
The trial will be conducted at more than 200 medical centers. As many as five to seven additional drugs may be evaluated over the next 5 years, the press release said. Information on enrolling patients can be found on the trial website.
A phase II/III trial using genomic profiling to match patients with investigational treatments is currently recruiting patients with advanced squamous cell lung cancer.
The Lung-MAP (Lung Cancer Master Protocol) trial is a public-private collaboration among the National Cancer Institute (NCI), SWOG Cancer Research, Friends of Cancer Research, the Foundation for the National Institutes of Health, Foundation Medicine, and five pharmaceutical companies (Amgen, Genentech, Pfizer, AstraZeneca, and AstraZeneca’s global biologics R&D arm, MedImmune).
"Lung-MAP represents the first of several planned large, genomically driven treatment trials that will be conducted by NCI’s newly formed National Clinical Trials Network (NCTN)," Dr. Jeffrey S. Abrams, associate director of NCI’s Cancer Therapy Evaluation Program, said in a press release announcing the trial launch. "The restructuring and consolidation of NCI’s large trial treatment program, resulting in the formation of the NCTN, is quite timely, as it now can offer an ideal platform for bringing the benefits of more precise molecular diagnostics to cancer patients in communities large and small, " he said.
Lung-MAP is expected to enroll 10,000 patients and be completed in 2022. To be eligible, patients will have progressed after receiving exactly one front-line, platinum-containing metastatic chemotherapy regimen. Between 500 and 1,000 patients will be screened per year for more than 200 cancer-related gene alterations. Based on the tumor profiles, all patients will then be assigned to one of five initial treatment arms, testing four investigational targeted treatments and an anti-PD-L1 immunotherapy.
The trial will be conducted at more than 200 medical centers. As many as five to seven additional drugs may be evaluated over the next 5 years, the press release said. Information on enrolling patients can be found on the trial website.
A phase II/III trial using genomic profiling to match patients with investigational treatments is currently recruiting patients with advanced squamous cell lung cancer.
The Lung-MAP (Lung Cancer Master Protocol) trial is a public-private collaboration among the National Cancer Institute (NCI), SWOG Cancer Research, Friends of Cancer Research, the Foundation for the National Institutes of Health, Foundation Medicine, and five pharmaceutical companies (Amgen, Genentech, Pfizer, AstraZeneca, and AstraZeneca’s global biologics R&D arm, MedImmune).
"Lung-MAP represents the first of several planned large, genomically driven treatment trials that will be conducted by NCI’s newly formed National Clinical Trials Network (NCTN)," Dr. Jeffrey S. Abrams, associate director of NCI’s Cancer Therapy Evaluation Program, said in a press release announcing the trial launch. "The restructuring and consolidation of NCI’s large trial treatment program, resulting in the formation of the NCTN, is quite timely, as it now can offer an ideal platform for bringing the benefits of more precise molecular diagnostics to cancer patients in communities large and small, " he said.
Lung-MAP is expected to enroll 10,000 patients and be completed in 2022. To be eligible, patients will have progressed after receiving exactly one front-line, platinum-containing metastatic chemotherapy regimen. Between 500 and 1,000 patients will be screened per year for more than 200 cancer-related gene alterations. Based on the tumor profiles, all patients will then be assigned to one of five initial treatment arms, testing four investigational targeted treatments and an anti-PD-L1 immunotherapy.
The trial will be conducted at more than 200 medical centers. As many as five to seven additional drugs may be evaluated over the next 5 years, the press release said. Information on enrolling patients can be found on the trial website.
