On March 4, 2015, the U. S. Food and Drug Administration granted approval to nivolumab (OPDIVO, Bristol-Myers Squibb Company) for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Nivolumab was previously approved in December, 2014 for the treatment of previously treated unresectable or metastatic melanoma. 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 anti-tumor immune response.
Approval was based on superior overall survival (OS) for patients who were randomly allocated to either nivolumab or docetaxel in an open-label, multicenter, multinational randomized trial in 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/m2 intravenously every 3 weeks. The major efficacy outcome was OS.
Nivolumab demonstrated a statistically significant improvement in OS as compared with docetaxel at the protocol pre-specified interim analysis. Median OS was 9.2 months (95% CI: 7.3, 13.3) for patients assigned to nivolumab and 6 months (95% CI: 5.1, 7.3) for those assigned to docetaxel [Hazard Ratio 0.59, 95% CI: 0.44, 0.79, p=0.00025].
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 (ORR) measured by independent review committee using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The ORR was 15% (95% CI: 9, 22) All were partial responses. At the time of analysis, 10 of the 17 responding patients (59%) had response durations of 6 months or longer.
The most common (greater than or equal to 30%) adverse reactions among the 117 patients receiving nivolumab in the above single-arm trial were fatigue, dyspnea, musculoskeletal pain, decreased appetite, and cough. The most frequent grade 3 and 4 adverse drug reactions observed in at least 5% of patients treated with nivolumab were dyspnea, fatigue, and musculoskeletal pain. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, nephritis/renal dysfunction, hypothyroidism, and hyperthyroidism.
The recommended dose of nivolumab is 3 mg/kg as an intravenous infusion over 60 minutes every 2 weeks.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125527s000lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).