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Opdivo Receives Expanded Lung Cancer Approval
Nivolumab (Opdivo, Bristol-Myers Squibb) has received FDA approval for use in the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. This expands its indication for previously treated metastatic squamous NSCLC to include nonsquamous patients.
Approval was granted based on results from the phase III CheckMate-057 trial, which demonstrated superior overall survival (OS) benefit for nivolumab versus docetaxel in previously treated metastatic NSCLC.
CheckMate-057 is a comparative study designed to demonstrate survival. Clinical results were recently presented at the 2015 European Cancer Congress with simultaneous publication in the New England Journal of Medicine. The open-label, randomized clinical trial evaluated nivolumab (3 mg/kg administered intravenously every two weeks, n = 292) versus docetaxel (75 mg/m2 administered intravenously every three weeks, n = 290) in patients with metastatic nonsquamous NSCLC who had experienced disease progression during or after one prior platinum doublet-based chemotherapy regimen. Appropriate targeted therapy may have been given to patients with known EGFR mutation or ALK translocation. The study included patients regardless of their PD-L1 (programmed death ligand-1) expression status. The primary endpoint of the trial was OS.
The median OS was 12.2 months in the nivolumab arm (95% confidence interval [CI], 9.7–15.0) and 9.4 months in the docetaxel arm (95% CI, 8.0–10.7). The hazard ratio (HR) was 0.73 (95% CI, 0.60–0.89; P = 0.0015), which translates to a 27% reduction in the risk of death with nivolumab compared to docetaxel. The prespecified interim analysis was conducted when 413 events were observed (93% of the planned number of events for final analysis).
Additional secondary endpoints include investigator-assessed objective response rate (ORR) and progression-free survival (PFS). The ORR in the nivolumab arm was 19% (56/292; four complete responses, 52 partial responses) (95% CI, 15–24) and 12% with docetaxel (36/290; one complete response, 35 partial responses) (95% CI, 9–17); P = 0.02. The median duration of response was 17 months in the nivolumab arm and 6 months in the docetaxel arm. Median PFS was 2.3 months in the nivolumab arm versus 4.2 months with docetaxel (HR = 0.92; 95% CI, 0.77–1.11; P = 0.39).
The safety profile of nivolumab in CheckMate-057 was consistent with prior studies. Serious adverse reactions occurred in 47% of patients receiving the medication. The most frequent serious adverse reactions in at least 2% of patients were pneumonia, pulmonary embolism, dyspnea, pleural effusions, and respiratory failure. Nivolumab was discontinued in 13% of patients and was delayed in 29% of patients for an adverse reaction. The most common adverse reactions (reported in at least 20% of patients) were fatigue (49%), musculoskeletal pain (36%), cough (30%), decreased appetite (29%), and constipation (23%).
Nivolumab is the only PD-1 therapy to have been studied in a phase III trial of patients with previously treated squamous NSCLC and a separate phase III trial of patients with previously treated nonsquamous NSCLC. Biomarker testing is not required for this product.
Source: BMS, October 9, 2015.