On March 4, 2022, the FDA accelerated the approval of the PD-1 inhibitor nivolumab (Opdivo; Bristol Myers Squibb) in combination with platinum-doublet chemotherapy for the neoadjuvant treatment of adults with resectable non–small-cell lung cancer (NSCLC). This represents the first FDA approval for neoadjuvant therapy for early-stage NSCLC.
The efficacy was evaluated in the CheckMate-816 study, a randomized, open-label clinical trial of patients with resectable, stage IB (≥4 cm), stage II, or stage IIIA NSCLC. Patients were enrolled regardless of the tumor PD-1 or PD-L1 status. A total of 358 patients were randomized to nivolumab plus platinum-doublet chemotherapy or to platinum-chemotherapy alone, administered every 3 weeks for up to 3 cycles in each arm.
The main efficacy outcomes were event-free survival (EFS) and pathologic complete response (pCR). The median EFS was 31.6 months (95% confidence interval [CI], 30.2-not reached) in the nivolumab plus chemotherapy arm and 20.8 months (95% CI, 14.0-26.7) in the chemotherapy-alone arm. The hazard ratio was 0.63 (97.38% CI, 0.43-0.91; P = .0052). The pCR rate was 24% (95% CI, 18.0-31.0) with nivolumab plus chemotherapy versus 2.2% (95% CI, 0.6-5.6) with chemotherapy alone.
The most common (≥20%) adverse reactions were nausea, constipation, fatigue, decreased appetite, and rash. The addition of nivolumab to chemotherapy did not lead to more frequent delays or cancellations of surgery. The median lengths of hospital days after definitive surgery, and the rates of adverse reactions related to surgery were similar in both groups.