NIVOLUMAB APPROVED BY FDA FOR SQUAMOUS NSCLC

The U.S. Food and Drug Administration (FDA) today approved the PD-1 inhibitor nivolumab (Opdivo) for the treatment of patients with metastatic squamous non–small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy. Nivolumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, thereby releasing PD-1 pathway–mediated inhibition of the immune response, including antitumor immune response.

Improved Overall Survival

The approval was based on the results of an open-label, multicenter, multinational randomized trial of 272 patients with metastatic squamous NSCLC who had experienced disease progression during or after one prior platinum-based chemotherapy regimen. Patients received nivolumab (n = 135) 3 mg/kg intravenously every 2 weeks or docetaxel (n = 137) 75 mg/m2intravenously every 3 weeks. The primary endpoint of the trial was overall survival.

Nivolumab demonstrated a statistically significant improvement in overall survival as compared with docetaxel at the protocol-prespecified interim analysis. Median overall survival was 9.2 months (95% confidence interval [CI] = 7.3–13.3) for patients receiving nivolumab and 6 months (95% CI = 5.1–7.3) for those receiving docetaxel (hazard ratio = 0.59, 95% CI = 0.44–0.79, P = .00025).

Approval was supported by a single-arm, multinational, multicenter trial in patients with metastatic squamous NSCLC who had progressed after receiving a platinum-based therapy and at least one additional systemic regimen. Patients (n = 117) received nivolumab 3 mg/kg intravenously every 2 weeks. The major efficacy outcome measure was confirmed objective response rate measured by an independent review committee using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The overall response rate was 15% (95% CI = 9%–22%), and all were partial responses. At the time of analysis, 10 of the 17 responding patients (59%) had response durations of 6 months or longer.

Side Effects

The most common side effects of nivolumab are fatigue, shortness of breath, musculoskeletal pain, decreased appetite, cough, nausea and, constipation. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lungs, colon, liver, kidneys, and hormone-producing glands.

Nivolumab for squamous NSCLC was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness in the treatment of a serious condition. The drug is being approved more than 3 months ahead of the prescription drug user fee goal date of June 22, 2015.

The FDA previously approved nivolumab to treat patients with unresectable or metastatic melanoma who no longer respond to other drugs.