Two new FDA approvals for cobimetinib (Cotellic, Roche) and ipilimumab (Yervoy, Bristol-Myers Squibb) for the treatment of melanoma mark the continuing advancement of melanoma research and innovation.
Combined Treatment
Cobimetinib was recently approved for the treatment of people with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma in combination with vemurafenib (Zelboraf, Genentech). Cobimetinib and vemurafenib are not used to treat melanoma with a normal BRAF gene.
“When used in combination, cobimetinib and vemurafenib help delay disease progression and help people live significantly longer than with vemurafenib alone,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech. “With this approval, people with this type of deadly and aggressive skin cancer now have a new targeted option.”
The FDA approval is based on results from the Phase III coBRIM study, which demonstrated cobimetinib plus vemurafenib reduced the risk of disease worsening or death (progression-free survival; PFS) by about half in people who received the combination (hazard ratio [HR]=0.56; 95% confidence interval [CI], 0.45-0.70; P<0.001), with a median PFS of 12.3 months for cobimetinib plus vemurafenib compared to 7.2 months with vemurafenib alone. An interim analysis also showed the combination of cobimetinib and vemurafenib helped people live significantly longer than vemurafenib alone (HR=0.63; 95% CI, 0.47-0.85; P=0.0019). The objective response rate (tumor shrinkage) was higher with cobimetinib plus vemurafenib compared to vemurafenib alone (70% vs 50%; P<0.001), as was the complete response rate (complete tumor shrinkage, 16% vs 10%).
Possible serious side effects with cobimetinib include risk of skin cancers, increased risk of bleeding, heart problems that can lead to inadequate pumping of the blood by the heart, rash, eye problems, abnormal liver test or liver injury, increased levels of an enzyme in the blood and photosensitivity. The most common side effects include diarrhea, sunburn or sun sensitivity, nausea, fever and vomiting. Cobimetinib can also cause changes in blood test results.
Adjunctive Therapy
In addition, ipilimumab recently received an expanded approval to include a new indication as adjuvant therapy for patients with stage III melanoma, to lower the risk that the melanoma will return following surgery.
“This approval of ipilimumab extends its use to patients who are at high risk of developing recurrence of melanoma after surgery,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. “This new use of the drug in earlier stages of the disease builds on our understanding of the immune system’s interaction with cancer.”
Ipilimumab, administered intravenously, was approved in 2011 to treat late-stage melanoma that cannot be removed by surgery. It is a monoclonal antibody that blocks the CTLA-4 (cytotoxic T-lymphocyte antigen) molecule. CTLA-4 may play a role in slowing down or turning off the body’s immune system, and affects its ability to fight off cancerous cells. Ipilimumab may work by allowing the body’s immune system to recognize, target and attack cells in melanoma tumors.
The safety and effectiveness of ipilimumab for this new use were studied in 951 patients who received ipilimumab or a placebo as adjuvant therapy following complete surgical removal of melanoma. The study measured the amount of time after treatment it took for the cancer to return and overall survival. Forty-nine percent of participants taking ipilimumab had their cancer return after an average of 26 months compared to 62% of those receiving a placebo, whose cancer returned after an average of 17 months. The analysis of overall survival data has not yet occurred.
The most common side effects of ipilimumab in this study were rash, diarrhea, fatigue, itching, headache, weight loss and nausea. Ipilimumab can also cause autoimmune disease in the digestive system, liver, skin, nervous system (which would each require treatment with corticosteroids) and in the hormone-producing glands (which requires life-long hormone replacement therapy). Women who are pregnant should not take ipilimumab because it may cause harm to a developing fetus. Due to the potential for fatal immune-mediated adverse reactions and unusual severe side effects with ipilimumab, the label includes a Boxed Warning.
For more insights and advances in melanoma diagnosis and treatment, see this month’s cover story here.
Two new FDA approvals for cobimetinib (Cotellic, Roche) and ipilimumab (Yervoy, Bristol-Myers Squibb) for the treatment of melanoma mark the continuing advancement of melanoma research and innovation.
Combined Treatment
Cobimetinib was recently approved for the treatment of people with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma in combination with vemurafenib (Zelboraf, Genentech). Cobimetinib and vemurafenib are not used to treat melanoma with a normal BRAF gene.
“When used in combination, cobimetinib and vemurafenib help delay disease progression and help people live significantly longer than with vemurafenib alone,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech. “With this approval, people with this type of deadly and aggressive skin cancer now have a new targeted option.”
The FDA approval is based on results from the Phase III coBRIM study, which demonstrated cobimetinib plus vemurafenib reduced the risk of disease worsening or death (progression-free survival; PFS) by about half in people who received the combination (hazard ratio [HR]=0.56; 95% confidence interval [CI], 0.45-0.70; P<0.001), with a median PFS of 12.3 months for cobimetinib plus vemurafenib compared to 7.2 months with vemurafenib alone. An interim analysis also showed the combination of cobimetinib and vemurafenib helped people live significantly longer than vemurafenib alone (HR=0.63; 95% CI, 0.47-0.85; P=0.0019). The objective response rate (tumor shrinkage) was higher with cobimetinib plus vemurafenib compared to vemurafenib alone (70% vs 50%; P<0.001), as was the complete response rate (complete tumor shrinkage, 16% vs 10%).
Possible serious side effects with cobimetinib include risk of skin cancers, increased risk of bleeding, heart problems that can lead to inadequate pumping of the blood by the heart, rash, eye problems, abnormal liver test or liver injury, increased levels of an enzyme in the blood and photosensitivity. The most common side effects include diarrhea, sunburn or sun sensitivity, nausea, fever and vomiting. Cobimetinib can also cause changes in blood test results.
Adjunctive Therapy
In addition, ipilimumab recently received an expanded approval to include a new indication as adjuvant therapy for patients with stage III melanoma, to lower the risk that the melanoma will return following surgery.
“This approval of ipilimumab extends its use to patients who are at high risk of developing recurrence of melanoma after surgery,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. “This new use of the drug in earlier stages of the disease builds on our understanding of the immune system’s interaction with cancer.”
Ipilimumab, administered intravenously, was approved in 2011 to treat late-stage melanoma that cannot be removed by surgery. It is a monoclonal antibody that blocks the CTLA-4 (cytotoxic T-lymphocyte antigen) molecule. CTLA-4 may play a role in slowing down or turning off the body’s immune system, and affects its ability to fight off cancerous cells. Ipilimumab may work by allowing the body’s immune system to recognize, target and attack cells in melanoma tumors.
The safety and effectiveness of ipilimumab for this new use were studied in 951 patients who received ipilimumab or a placebo as adjuvant therapy following complete surgical removal of melanoma. The study measured the amount of time after treatment it took for the cancer to return and overall survival. Forty-nine percent of participants taking ipilimumab had their cancer return after an average of 26 months compared to 62% of those receiving a placebo, whose cancer returned after an average of 17 months. The analysis of overall survival data has not yet occurred.
The most common side effects of ipilimumab in this study were rash, diarrhea, fatigue, itching, headache, weight loss and nausea. Ipilimumab can also cause autoimmune disease in the digestive system, liver, skin, nervous system (which would each require treatment with corticosteroids) and in the hormone-producing glands (which requires life-long hormone replacement therapy). Women who are pregnant should not take ipilimumab because it may cause harm to a developing fetus. Due to the potential for fatal immune-mediated adverse reactions and unusual severe side effects with ipilimumab, the label includes a Boxed Warning.
For more insights and advances in melanoma diagnosis and treatment, see this month’s cover story here.
Two new FDA approvals for cobimetinib (Cotellic, Roche) and ipilimumab (Yervoy, Bristol-Myers Squibb) for the treatment of melanoma mark the continuing advancement of melanoma research and innovation.
Combined Treatment
Cobimetinib was recently approved for the treatment of people with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma in combination with vemurafenib (Zelboraf, Genentech). Cobimetinib and vemurafenib are not used to treat melanoma with a normal BRAF gene.
“When used in combination, cobimetinib and vemurafenib help delay disease progression and help people live significantly longer than with vemurafenib alone,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech. “With this approval, people with this type of deadly and aggressive skin cancer now have a new targeted option.”
The FDA approval is based on results from the Phase III coBRIM study, which demonstrated cobimetinib plus vemurafenib reduced the risk of disease worsening or death (progression-free survival; PFS) by about half in people who received the combination (hazard ratio [HR]=0.56; 95% confidence interval [CI], 0.45-0.70; P<0.001), with a median PFS of 12.3 months for cobimetinib plus vemurafenib compared to 7.2 months with vemurafenib alone. An interim analysis also showed the combination of cobimetinib and vemurafenib helped people live significantly longer than vemurafenib alone (HR=0.63; 95% CI, 0.47-0.85; P=0.0019). The objective response rate (tumor shrinkage) was higher with cobimetinib plus vemurafenib compared to vemurafenib alone (70% vs 50%; P<0.001), as was the complete response rate (complete tumor shrinkage, 16% vs 10%).
Possible serious side effects with cobimetinib include risk of skin cancers, increased risk of bleeding, heart problems that can lead to inadequate pumping of the blood by the heart, rash, eye problems, abnormal liver test or liver injury, increased levels of an enzyme in the blood and photosensitivity. The most common side effects include diarrhea, sunburn or sun sensitivity, nausea, fever and vomiting. Cobimetinib can also cause changes in blood test results.
Adjunctive Therapy
In addition, ipilimumab recently received an expanded approval to include a new indication as adjuvant therapy for patients with stage III melanoma, to lower the risk that the melanoma will return following surgery.
“This approval of ipilimumab extends its use to patients who are at high risk of developing recurrence of melanoma after surgery,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. “This new use of the drug in earlier stages of the disease builds on our understanding of the immune system’s interaction with cancer.”
Ipilimumab, administered intravenously, was approved in 2011 to treat late-stage melanoma that cannot be removed by surgery. It is a monoclonal antibody that blocks the CTLA-4 (cytotoxic T-lymphocyte antigen) molecule. CTLA-4 may play a role in slowing down or turning off the body’s immune system, and affects its ability to fight off cancerous cells. Ipilimumab may work by allowing the body’s immune system to recognize, target and attack cells in melanoma tumors.
The safety and effectiveness of ipilimumab for this new use were studied in 951 patients who received ipilimumab or a placebo as adjuvant therapy following complete surgical removal of melanoma. The study measured the amount of time after treatment it took for the cancer to return and overall survival. Forty-nine percent of participants taking ipilimumab had their cancer return after an average of 26 months compared to 62% of those receiving a placebo, whose cancer returned after an average of 17 months. The analysis of overall survival data has not yet occurred.
The most common side effects of ipilimumab in this study were rash, diarrhea, fatigue, itching, headache, weight loss and nausea. Ipilimumab can also cause autoimmune disease in the digestive system, liver, skin, nervous system (which would each require treatment with corticosteroids) and in the hormone-producing glands (which requires life-long hormone replacement therapy). Women who are pregnant should not take ipilimumab because it may cause harm to a developing fetus. Due to the potential for fatal immune-mediated adverse reactions and unusual severe side effects with ipilimumab, the label includes a Boxed Warning.
For more insights and advances in melanoma diagnosis and treatment, see this month’s cover story here.
