Frontline Nivolumab Approved for BRAF Wild-type Melanoma

November 24, 2015

Today the FDA approved the PD-1 inhibitor nivolumab (Opdivo) as a single-agent frontline treatment for patients with BRAF wild-type advanced melanoma.

Today the US Food and Drug Administration (FDA) approved the PD-1 inhibitor nivolumab (Opdivo) as a single-agent frontline treatment for patients with BRAF wild-type advanced melanoma, according to the drug’s manufacturer Bristol-Myers Squibb.

The approval of nivolumab was based on efficacy results from the CheckMate-066 trial. The trial included 418 patients who were randomly assigned to nivolumab (3 mg/kg every 2 weeks) or dacarbazine (1,000 mg/m2 every 3 weeks). The primary endpoint of the study was overall survival.

Patients assigned to nivolumab had significantly improved overall survival compared with dacarbazine, according to the results of an interim analysis of the trial that included 47% of the total planned events. The median overall survival was not reached for patients assigned nivolumab compared with 10.8 months for patients assigned dacarbazine (hazard ratio [HR], 0.42; P < .0001).

“Advanced melanoma continues to be one of the deadliest and most challenging cancers to treat, and ongoing research in immuno-oncology from clinical trials like CheckMate-066 shows the potential to provide improved overall survival for newly diagnosed patients with BRAF wild-type metastatic melanoma,” said Jeffrey S. Weber, MD, PhD, deputy director of the Laura and Isaac Perlmutter Cancer Center at the NYU Langone Medical Center, in a statement. “This important news means that we now have another new option to offer patients with BRAF wild-type metastatic melanoma.”

Secondary endpoints of CheckMate-066 included progression-free survival and overall response rate. Patients assigned nivolumab had twice the median progression-free survival compared with the dacarbazine group (5.1 vs 2.2 months; HR for death or progression, 0.43; P < .001). The objective response rate was 34% for patients assigned nivolumab compared with 9% for patients assigned dacarbazine (P < .001). According to the manufacturer, at the time of the interim analysis, 88% of patients who initially responded to nivolumab had ongoing responses.

Patients assigned nivolumab did experience adverse reactions (36%), including grade 3 or 4 adverse events (41%). The most common grade 3 or 4 adverse events were gamma-glutamyl transferase increase (3.9%) and diarrhea (3.4%). Adverse events caused 7% of patients assigned to nivolumab to discontinue treatment and caused dose interruptions in 26% of patients.

In September, nivolumab was also granted accelerated approval with ipilimumab for patients with BRAF wild-type advanced melanoma. The drug was also approved yesterday for the treatment of advanced renal cell carcinoma and was approved for nonsmall-cell lung cancer earlier this year.