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Nivolumab (Opdivo) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of lung cancer on March 4, 2015, before clinical data from the pivotal trials (CheckMate 017 and CheckMate 063) were presented at a major oncology conference or published in a peer-reviewed journal. Data from CheckMate 063 have since been published.1 Data from CheckMate 017 were shared with health authorities in December 2014, according to the manufacturer, Bristol-Myers Squibb, and the company plans to work with investigators toward future presentation and publication of the results from CheckMate 017.

CheckMate 017: Survival Benefit

CheckMate 017 was an open-label, randomized phase III study evaluating nivolumab (3 mg/kg intravenously over 60 minutes every 2 weeks) (n = 135) vs docetaxel (75 mg/m2 intravenously administered every 3 weeks), in previously treated patients (n = 137) with advanced, squamous cell non–small cell lung cancer (NSCLC). This trial included patients regardless of their tumor’s programmed death ligand 1 (PD-L1) status. The primary endpoint of this trial was overall survival. The trial was stopped early because an assessment conducted by the independent data monitoring committee concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving nivolumab.

In patients receiving nivolumab, the median overall survival was 9.2 months (95% confidence interval [CI] = 7.3–13.3 months) vs 6 months in patients receiving docetaxel (95% CI = 5.1–7.3 months). The hazard ratio was 0.59 (95% = 0.44–0.79; P = .00).

CheckMate 063: Safety and Efficacy

The safety profile of nivolumab in squamous NSCLC was established in CheckMate 063, a phase II single-arm, open-label, multinational, multicenter trial of nivolumab, administered as a single agent in patients with metastatic squamous NSCLC with disease progression after receiving a platinum-based therapy and at least one additional systemic treatment regimen (n = 117). Patients received 3 mg/kg of nivolumab administered intravenously over 60 minutes every 2 weeks. This trial included patients regardless of the PD-L1 status of their tumor.

The most common adverse reactions were fatigue (50%), dyspnea (38%), musculoskeletal pain (36%), decreased appetite (35%), cough (32%), nausea (29%), and constipation (24%). Serious adverse reactions occurred in 59% of patients receiving nivolumab. The most frequent serious adverse reactions reported in ≥ 2% of patients were dyspnea, pneumonia, chronic obstructive pulmonary disease exacerbation, pneumonitis, hypercalcemia, pleural effusion, hemoptysis, and pain.

Adverse reactions resulted in drug discontinuation in 27% and drug delay in 29% of patients. 

Accelerated Drug Approval

In a related news release, Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said, “The FDA worked proactively with [Bristol-Myers Squibb] to facilitate the early submission and review of this important clinical trial when results first became available in late December 2014.” Dr. Pazdur told The ASCO Post that the FDA believes prescribing should be based on a product’s label. The product label for nivolumab is available at ■


1. Rizvi NA, Mazieres J, Planchard D, et al: Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced refractory squamous non-small-cell lung cancer (CheckMate 063): A phase 2, single-arm trial. Lancet Oncol 16:257-265, 2015.


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