FDA Approval Summary: Nivolumab for the Treatment of Metastatic Non-Small Cell Lung Cancer With Progression On or After Platinum-Based Chemotherapy. (16th March 2016)

• Record Type: Journal Article
• Authors: Kazandjian, Dickran; Suzman, Daniel L.; Blumenthal, Gideon; Mushti, Sirisha; He, Kun; Libeg, Meredith; Keegan, Patricia; Pazdur, Richard
• Is Part Of: Oncologist. Volume 21:Number 5(2016)
• Page Start: 634
• Page End: 642
• Publication Date: 2016-03-16
• Subjects: Nivolumab -- Non-small cell lung carcinoma -- PD-1 inhibitor -- Immunotherapy; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2015-0507
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: On October 9, 2015, the U.S. Food and Drug Administration expanded the nivolumab metastatic non-small cell lung cancer (NSCLC) indication to include patients with nonsquamous NSCLC after a 3.25-month review timeline. Approval was based on demonstration of an improvement in overall survival (OS) in an international, multicenter, open-label, randomized trial comparing nivolumab to docetaxel in patients with metastatic nonsquamous NSCLC with progression on or after platinum-based chemotherapy. The CheckMate 057 trial enrolled 582 patients who were randomized (1:1) to receive nivolumab or docetaxel. Nivolumab demonstrated improved OS compared with docetaxel at the prespecified interim analysis with a hazard ratio (HR) of 0.73 ( p = .0015), and a median OS of 12.2 months (95% CI: 9.7–15.0 months) in patients treated with nivolumab compared with 9.4 months (95% CI: 8.0–10.7 months) in patients treated with docetaxel. A statistically significant improvement in objective response rate (ORR) was also observed, with an ORR of 19% (95% CI: 15%–24%) in the nivolumab arm and 12% (95% CI: 9%–17%) in the docetaxel arm. The median duration of response was 17 months in the nivolumab arm and 6 months in the docetaxel arm. Progression-free survival was not statistically different between arms. A prespecified retrospective subgroup analysis suggested that patients with programmed cell death ligand 1-negative tumors treated with nivolumab had similar OS to those treated with docetaxel. The toxicity profile of nivolumab was consistent with the known immune-mediated adverse event profile except for 1 case of grade 5 limbic encephalitis, which led to a postmarketing requirement study to better characterize immune-mediated encephalitis. Abstract : In the CheckMate 057 trial, an international, multicenter, open-label, randomized trial in patients with metastatic nonsquamous non-small cell lung cancer with progression on or after platinum-based chemotherapy, improved overall survival and objective response rates were demonstrated with nivolumab compared with docetaxel. Progression-free survival did not differ between the two arms of the study.