Due to the early and overwhelmingly positive results, the vemurafenib study was stopped early and patients in the dacarbazine arm were allowed to cross over and receive the Roche drug.
Fewer than 10 percent of patients who received vemurafenib experienced problems with high levels of toxicity, grade three or worse. The most common side effects were skin rashes, photosensitivity, and joint pain. About 12% patients developed a low-grade skin cancer, squamous cell carcinoma, but once removed, patients could continue treatment with vemurafenib.
Bristol's Yervoy belongs to a new class of drugs that harness a patient's own immune system to target and fight cancer. Yervoy is an antibody that targets cytotoxic T-lymphocyte associated antigen (CTLA-4), which acts like a brake on the T-cell, a key component of the immune system. Yervoy removes this brake, enabling a patient's own T cells to attack the cancer.
Yervoy was approved in March to treat patients with advanced metastatic melanoma that was no longer responding to previous treatments. The study being highlighted at ASCO this year demonstrates Yervoy's ability to prolong survival in previously untreated melanoma patients.
In this study, 502 patients with metastatic melanoma were randomized to treatment with Yervoy plus the chemotherhapy drug dacarbazine or placebo and dacarbazine. The Yervoy-chemotherapy treatment resulted in a 28% reduction in the risk of death compared to the chemotherapy alone treatment.
The overall survival rate for the Yervoy combination after one year was 47.3% compared to 36.3% for dacarbazine alone. After two years, the overall survival rate was 28.5% for the Yervoy combination versus 17.9 percent for dacarbazine alone. At three years, overall survival was 20.8% for the combination compared to 12.2% for chemotherapy alone.
"This trial's three-year endpoint is significant. No randomized trial for metastatic melanoma has followed patients for this long, and it demonstrates the durability of this survival benefit, now out to three years in this population, and even four years in some cases," said Dr. Jedd Wolchok of Memorial Sloan-Kettering Cancer Center in New York.
Wolchok added, "It's one of the advantages of immunotherapy. The immune system is a 'living drug,' able to adapt itself to changes in the tumor that might otherwise lead to resistance when treated with chemotherapy or a pathway inhibitor."