FDA Approves Nivolumab for Advanced Melanoma

Posted on December 23rd, 2014 by

The FDA granted accelerated approval to nivolumab (Opdivo) for patients with unresectable or metastatic melanoma who no longer respond to other drugs. Nivolumab, a PD-1 inhibitor, is intended for patients who have been previously treated with ipilimumab (Yervoy) and, for melanoma patients whose tumors express the BRAF V600 mutation, for use after treatment with ipilimumab and a BRAF inhibitor.

The immunotherapy drug nivolumab produces significantly better overall survival than chemotherapy as initial treatment in advanced melanoma, according to findings from its first Phase III study in previously untreated patients. These results were recently published online in the New England Journal of Medicine.[1]

Of the more than one million new diagnoses of skin cancer each year, roughly 68,000 involve melanoma. More than 8,000 people die of melanoma each year in the United States. Melanoma is dangerous because it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.

Nivolumab belongs to a new class of medicines called PD-1 inhibitors that have generated great excitement for their ability to help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 may enhance the ability of the immune system to fight cancer. Nivolumab works by blocking PD-1.

A randomized Phase III clinical trial called CheckMate -066 has been evaluating nivolumab as initial, or first line, therapy for patients with advanced melanoma without a mutation in the BRAF gene (a protein that is involved in sending signals in cells and in cell growth). Earlier this year an interim analysis of CheckMate -066, performed by an independent data-monitoring committee, found evidence of superior overall survival in patients receiving nivolumab compared with those who received the chemotherapy dacarbazine. The committee stopped the study early to allow the dacarbazine patients to switch nivolumab.[2]

When CheckMate -066 was halted early, researchers planned to complete a full evaluation of trial data and present their findings at a later date. Those results are now available and confirm superior survival rates among patients who received nivolumab compared with chemotherapy.

The trial included 418 patients with advanced melanoma without a BRAF mutation. Participants had not been previously treated for melanoma. They were assigned to receive one of two treatments:

  • Nivolumab every two weeks plus a placebo for the chemotherapy dacarbazine, or
  • Dacarbazine every three weeks plus a placebo for nivolumab every two weeks

At one year, survival was significantly better in the nivolumab group compared with the dacarbazine group:

  • Almost 73% of patients in the nivolumab group were alive, compared with 42% in the dacarbazine group.
  • Median progression-free survival more than doubled among patients receiving nivolumab: just over five months compared with just over two months for dacarbazine.
  • Treatment response also more the doubled for patients receiving nivolumab: 40% responded to treatment compared with just 14% in the dacarbazine group.
  • Side effects with nivolumab included fatigue, itching, and nausea.

According to Caroline Robert, Professor of Dermatology, Head of the Dermatology Unit, Institute Gustave, and lead author of the New England Journal of Medicine manuscript, “The results from CheckMate -066 are significant as they represent the first time a PD-1 immune checkpoint inhibitor has shown a survival benefit in a randomized Phase 3 trial.” She called these findings “a major milestone” in research into first-line treatment of advanced melanoma without a BRAF mutation.[3]

References:

[1] Robert C, Long GV, Brady B, et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. New England Journal of Medicine [early online publication]. November 16, 2014.

[2] Topalian SL, Sznol M, McDermott DF, et al. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal of Clinical Oncology [early online publication]. March 3, 2014. doi: 10.1200/JCO.2013.53.0105.

[3] Study Comparing Opdivo (nivolumab) to Chemotherapy in Treatment Naïve Advanced Melanoma Patients Marks First PD-1 Immune Checkpoint Inhibitor to Demonstrate a Survival Benefit in a Phase 3 Trial [press release]. Bristol-Myers Squibb website. Available at: http://news.bms.com/press-release/study-comparing-opdivo-nivolumab-chemotherapy-treatment-naive-advanced-melanoma-patien&t=635517264951231587. Accessed November 17, 2014.

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Tags: fda, Melanoma, News, nivolumab, opdivo, PD-1, Recurrent Melanoma, Stage IV Melanoma

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