Nivolumab, a programmed death receptor–1 (PD-1) blocking antibody, has been approved as a single agent for the first-line treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma, the manufacturer has announced.
The approval is based on the results of a phase III study, CheckMate 066, which found a significant overall survival (OS) benefit for nivolumab, compared with chemotherapy, as a first-line treatment of patients with BRAF wild-type advanced melanoma, according to a press release issued by Bristol Myers Squibb (BMS) on Nov. 24.
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The company markets nivolumab as Opdivo, which was first approved by the Food and Drug Administration in December 2014 for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab (Yervoy) treatment and, if BRAF V600 mutation positive, a BRAF inhibitor.
OS was the primary endpoint in the CheckMate 066 trial, which compared treatment with nivolumab (3mg/kg administered intravenously every 2 weeks) to dacarbazine (1,000 mg/m2 administered intravenously every 3 weeks) administered in 418 treatment-naive patients with BRAF wild-type unresectable or metastatic melanoma. In an interim analysis, the median OS for those on dacarbazine was 10.8 months, but was not reached for those on nivolumab (hazard ratio, 0.42; P less than .0001), according to BMS.
The study was stopped early in 2014, after the OS results were noted, the company statement said. At the time the study was designed, ipilimumab had not yet been approved, and dacarbazine was chosen as the comparator because “it represented the standard of care in many regions outside of the U.S.,” the statement added.
Other results included a significantly greater median PFS among those on nivolumab vs. dacarbazine (5.1 months vs. 2.2 months).
In the study, 36% of nivolumab-treated patients had serious adverse reactions; and 41% had grade 3 and 4 adverse reactions, the most common included an increase in gamma-glutamyl transferase in almost 4%, and diarrhea in 3.4%. In addition, 7% stopped treatment permanently because of adverse events, and treatment had to be interrupted in 26%.
The most common adverse reactions reported by those on nivolumab included fatigue, in 49% (vs. 39% of those on dacarbazine) and musculoskeletal pain in 32% (vs. 25%). Rash and pruritus were reported by 28% and 23%, respectively, among those on nivolumab vs. 12% for both rash and pruritus among those on dacarbazine, BMS said.