Pipeline Series: Melanoma

The American Cancer Society estimates that approximately 76 380 new melanomas will be diagnosed in the United States in 2016 and about 10 130 patients will die from the disease. Although melanoma accounts for only 1% of skin cancer cases, the rates of melanoma have been rising for at least the last 30 years and causes most skin cancer deaths.¹

Immunotherapies and kinase inhibitors have drastically evolved the treatment landscape for metastatic or unresectable melanoma. In only the last 5 years, the U.S. Food and Drug Administration has approved ipilimumab, vemurafenib, pembrolizumab, dabrafenib, trametinib, cobimetinib, and nivolumab. The National Comprehensive Cancer Network (NCCN) guidelines for melanoma treatment recommend all of the aforementioned agents as first-line therapy, some as single-agents and others in combination with each other.²

The melanoma treatment pipeline includes additional targeted therapies and immunotherapies that have already demonstrated safety and efficacy in phase 2 and 3 trials. Cancer Therapy Advisor spoke with Ryan J. Sullivan, MD, medical oncologist at Massachusetts General Hospital in Boston, MA, to gain his insight into which therapies he believes are the most important in the future of melanoma treatment.

Binimetinib

Binimetinib is a small molecule MEK inhibitor that targets key enzymes in the RAS/RAF/MEK/ERK pathway, which regulates numerous vital cellular activities including proliferation, differentiation, migration, survival, and angiogenesis.³

“Binimetinib by itself is looking like a potentially important treatment for NRAS-mutant melanoma,” said Dr Sullivan, who specializes in the treatment of melanoma and has been involved in a number of studies involving kinase inhibitors and immunotherapies.

An ongoing phase 3 clinical trial of binimetinib demonstrated that binimetinib improved median progression-free survival by 1.3 months compared with dacarbazine in patients with advanced NRAS-mutant melanoma. Further, the study demonstrated that binimetinib was generally well tolerated.³

For the international NEMO trial, researchers enrolled 402 patients with advanced NRAS-mutant melanoma and randomly assigned them 2:1 to receive binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m² intravenously every 3 weeks.

Binimetinib is also being evaluated in patients with BRAF-mutant melanoma in the phase 3 COLUMBUS study, as well as in combination with ribociclib, an oral selective CDK4/6 inhibitor.