New immunotherapy drugs for patients with metastatic melanoma

This review presents the results of clinical trials for two newly approved immunotherapy drugs – ipilimumab (Yervoy) and vemurafenib (Zelboraf) – used for the treatment of patients with metastatic (late stage or advanced) melanoma.

Metastatic melanoma (MM) is cancer of the pigmented (colored) cells of the skin (or "melanocytes") that has spread to distant lymph nodes or other organs of the body. Treatment for this stage of melanoma may include surgery, chemotherapy, radiotherapy and immunotherapy (biological therapy). Immunotherapy stimulates the patient’s own immune system to recognize and destroy cancer cells.

Ipilimumab (Yervoy) and Vemurafenib (Zelboraf) are two new immunotherapy drugs approved by the US FDA and by the European Medicines Agency (EMA) for the treatment of patients with MM. Ipilimumab works by activating the immune system to recognize, target and destroy melanoma cells. Vemurafenib works for melanomas with a specific genetic mutation in the BRAF gene. About 50% of melanomas have this genetic mutation. Blocking the BRAF protein with this drug can help stop the cancer's growth.

The approval of these two drugs was based on the results of several clinical trials. The article reviews 2 clinical trials that tested the safety and efficacy of ipilimumab: first as monotherapy (ipilimumab alone) for patients that were previously treated for MM, and second, in combination with chemotherapy (dacarbazine), as first line therapy (the first treatment for a disease). As monotherapy, ipilimumab extended overall survival for MM patients by 34%. In the second trial, patients who received ipilimumab and dacarbazine had a 28% longer overall survival rate and a 24% longer period without the cancer progressing (progression-free survival) compared to patients who received dacarbazine alone. 

Vemurafenib was approved based on the results of a phase III clinical trial that included patients with MM and BRAF mutations. These patients received either vemurafenib or chemotherapy (dacarbazine). The overall survival 6 months after treatment was longer for patients treated with vemurafenib compared to those who received dacarbazine (84% versus 64%). The most common side effects due to vemurafenib therapy were skin rashes, joint pain and fatigue.

In summary, these new immunotherapy drugs show important survival benefits for patients with MM. Vemurafenib is useful for patients with BRAF mutations, whereas ipilimumab can be used in all MM patients.

Further studies are needed to determine how these newly approved therapies can be used in clinical practice in order for melanoma patients to get the best treatment for their disease.