The Food and Drug Administration (FDA) has approved the combination of Opdivo (nivolumab; Bristol Myers Squibb) plus Yervoy (ipilimumab; Bristol Myers Squibb) for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. A companion diagnostic test, PD-L1 IHC 28-8 pharmDx (Agilent Technologies), was also granted approval for helping to select patients for treatment with the combination therapy.
The approval was based on data from the CHECKMATE-227 trial, an open-label, multi-part study that included patients with histologically confirmed Stage IV or recurrent NSCLC, ECOG performance status 0 or 1, and no prior anticancer therapy. In Part 1a of the phase 3 trial, a total of 793 patients were randomized to receive either nivolumab in combination with ipilimumab (n=396) or platinum-doublet chemotherapy (n=397).
Results showed a statistically significant improvement in overall survival (primary efficacy outcome measure) for PD-L1 ≥1% patients in the nivolumab plus ipilimumab arm compared with the platinum doublet-chemotherapy arm (hazard ratio [HR] 0.79; 95% CI, 0.67-0.94; P =.0066) with a minimum follow up of 29.3 months. Median overall survival was 17.1 months (95% CI, 15.0-20.1) with nivolumab plus ipilimumab vs 14.9 months (95% CI, 12.7-16.7) with platinum doublet-chemotherapy.
Study findings also showed that 63%, 40%, and 33% of patients treated with nivolumab plus ipilimumab were alive at 1, 2, and 3 years, respectively, compared with 56%, 33%, and 22% of patients treated with chemotherapy. The Blinded Independent Central Review-assessed confirmed overall response rate was 36% (95% CI, 31-41) in the nivolumab plus ipilimumab arm and 30% (95% CI, 26-35) in the chemotherapy arm. Median duration of response was observed to be 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy.
With regard to safety, the most common adverse reactions in patients receiving the combination in CHECKMATE-227 included fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.
“The results from the CheckMate-227 trial show that a dual immunotherapy approach offers a chance at long-term survival for appropriate patients with metastatic NSCLC,” said Matthew D. Hellmann, MD, CheckMate-227 study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center.
The combination of nivolumab, a programmed death receptor-1 blocking antibody, and ipilimumab, a human cytotoxic T-lymphocyte antigen 4-blocking antibody, has also been approved for the treatment of unresectable or metastatic melanoma; for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma; for the treatment of microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer (CRC); and for the treatment of hepatocellular carcinoma (HCC) in patients previously treated with sorafenib.
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