NEW DRUG APPROVALS Opdivo for Melanoma

NEW DRUG APPROVALS Opdivo for Melanoma Nivolumab injection (Opdivo, BristolMyers Squibb) has received the FDA’s accelerated approval for the treatment of patients with unresectable or metastatic melanoma that has progressed after treatment with specific medications. Nivolumab is a monoclonal antibody that binds to the programmed death-1 (PD-1) receptor and blocks its interaction with ligands PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response. It is indicated for intravenous treatment of patients with disease progression after treatment using ipilimumab (Yervoy, Bristol-Myers Squibb) and, in cases of BRAF V600 mutation-positive disease, a BRAF inhibitor. Accelerated approval was based on the tumor response rate and the durability of response. Nivolumab is associated with immunemediated pneumonitis, colitis, hepatitis, nephritis, renal dysfunction, hypothyroidism, hyperthyroidism, and embryofetal toxicity, among other adverse reactions. Nivolumab’s efficacy was evaluated in a single-arm, noncomparative planned interim analysis of the first 120 patients who received the drug with at least six months’ follow-up in CheckMate-037, a pivotal, randomized, phase 3 clinical trial in advanced melanoma that had progressed on ipilimumab and (if BRAF mutation-positive) a BRAF inhibitor. CheckMate-037 compared nivolumab 3 mg/kg (n = 268), administered every two weeks, with chemotherapy (n = 102) consisting of the investigator’s choice of either single-agent dacarbazine 1 g/m2 every three weeks or the combination of carboplatin AUC 6 every three weeks plus paclitaxel 175 mg/m2 every three weeks. The primary endpoint was the objective response rate (ORR). In the interim analysis of 120 nivolumab-treated patients, 76% had advanced metastatic disease; 18% had a history of brain metastases. Their median age was 58 years, and 22% were BRAF V600 mutation-positive. Nivolumab achieved a 32% response rate (38 of 120). Four patients (3%) showed a complete response, and 34 (28%) showed a partial response. Of these 38 patients 87% had ongoing responses ranging from 2.6-plus to 10-plus months. Responses to nivolumab were demonstrated in patients with or without the BRAF mutation. In CheckMate-037, serious adverse events (AEs) occurred in 41% of the patients treated with nivolumab. The most frequent grade-3 and grade-4 AEs (reported in 2% to less than 5% of patients) included abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. The most common AE was rash (21%). Sources: Bristol-Myers Squibb and FDA, December 22, 2014