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Opdivo Receives FDA Approval to Treat More Cases of Advanced Melanoma

The drug is now a first-line single agent for advanced BRAF wild-type melanoma

The FDA has approved the expanded use of nivolumab (Opdivo, Bristol-Myers Squibb) to treat an additional form of advanced skin cancer.

Intravenous nivolumab can be used as a single agent for the treatment of patients with BRAF V600 wild-type (WT) unresectable or metastatic melanoma. The approval is based on data from a phase 3 trial, CheckMate-066, which evaluated overall survival (OS) as the primary endpoint in treatment-naïve patients with BRAF WT unresectable or metastatic melanoma compared to chemotherapy (dacarbazine).

“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 New York University Langone Medical Center.

CheckMate-066 is a randomized, double-blind study of treatment-naïve patients with unresectable or metastatic BRAF WT melanoma. Patients were randomized to receive nivolumab (3 mg/kg intravenously every two weeks; n = 210) or dacarbazine (1,000 mg/m2 intravenously every three weeks; n = 208). The primary efficacy endpoint of the trial was OS, and secondary endpoints were progression-free survival (PFS) and objective response rate (ORR).

Nivolumab demonstrated superior OS versus chemotherapy in the first-line setting. Results were based on the interim analysis conducted on 47% of the total planned events for OS (50 for the nivolumab arm, 96 for the dacarbazine arm). The median OS was not reached for Opdivo and was 10.8 months (95% confidence interval [CI], 9.3–12.1) in the dacarbazine arm (hazard ratio [HR], 0.42; 95% CI, 0.30–0.60; P < 0.0001).

Median PFS more than doubled with nivolumab (5.1 months [95% CI, 3.5–10.8] versus 2.2 months [95% CI, 2.1–2.4] for patients treated with dacarbazine [HR, 0.43; 95% CI, 0.34–0.56; P < 0.0001]). ORR with nivolumab was 34% (4% complete response rate, 30% partial response rate [95% CI, 28–41]) compared to 9% with dacarbazine (1% complete response rate, 8% partial response rate [95% CI, 5–13]). At the time of analysis, 88% (63 of 72) of nivolumab-treated patients had ongoing responses, which included 43 patients with ongoing responses of six months or longer.

Last year, the CheckMate-066 trial was stopped early following a recommendation by the independent Data Monitoring Committee based on an analysis that showed evidence of superior OS in patients receiving nivolumab compared to the control arm. As a result, patients in the trial were unblinded and those who had received dacarbazine were allowed to receive nivolumab. Dacarbazine was selected as the comparator in this study because, at the time the study protocol was designed, it represented the standard of care in many regions outside of the U.S. where Yervoy had not yet been approved for first-line use.

In the trial, serious adverse reactions occurred in 36% of patients receiving nivolumab. Grade 3 and 4 adverse reactions occurred in 41% of patients receiving nivolumab. The most frequent Grade 3 and 4 adverse reactions reported in at least 2% of patients receiving nivolumab were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). Adverse reactions led to permanent discontinuation of nivolumab in 7% of patients and dose interruption in 26% of patients. The most common adverse reactions in CheckMate-066 (more than 20%) reported with nivolumab versus dacarbazine were fatigue (49% versus 39%), musculoskeletal pain (32% versus 25%), rash (28% versus 12%), and pruritus (23% versus 12%).

Nivolumab has been associated with immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, and encephalitis; other adverse reactions; infusion reactions; and embryofetal toxicity.

Source: Bristol-Myers Squibb, November 24, 2015.

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