FDA Approves Combination Therapy for Treatment of Melanoma

On October 1, 2015, The US Food and Drug Administration (FDA) announced approval of the combined usage of two chemotherapeutic agents,Opdivo(nivolumab) andYervoy (ipilimumab), both from Bristol-Myers-Squibb, for treatment of metastatic melanoma exhibiting theBRAFV600 wildtype.

According to Medscape, although combination chemotherapy is controversial among experts in the field, results of clinical trialCheckMate069showed significant differences in outcomes when the combination of nivolumab and ipilimumab went head-to-head against ipilimumab alone. In patients with BRAF wildtype melanoma, the objective response rate favored the combination 60% vs 11%. Complete and partial responses were also higher with the combination with values of 17% vs 0% and 43% vs 11% respectably. Additionally, the risk for progression was 60% lower with the combination in comparison to monotherapy. Median progression free survival was 8.9 months with the combination and 4.7 months with ipilimumab alone.

The controversy of using combination chemotherapy is based on two main factors: cost and toxicity. Study observers caution that the cost of the combination of nivolumab and ipilimumab is nearly $300,000. In addition, individual chemotherapeutic agents carry an array of adverse side effects and so combining them can double the toxicity. Not surprisingly, adverse reactions within the group taking the combination in CheckMate069 had a higher rate of occurrence than in the monotherapy group. The most common serious adverse reactions of the combination were colitis, diarrhea, pyrexia, and pneumonitis.

This approval marks a milestone in oncology as it steers in the direction of combination therapy for the future. Combination therapy does not come without its challenges as pointed out by both Frances Collichio, MD, from the University of North Carolina in Chapel Hill and Jedd Wolchok, MD, PhD, from the Memorial Sloan Kettering Cancer Center in New York City who stated that since we cannot afford to treat everyone with expensive combination therapy, it is imperative to find the optimal patient.