On March 4, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo) in combination with platinum-doublet chemotherapy for adult patients with resectable non–small cell lung cancer (NSCLC) in the neoadjuvant setting. This represents the first FDA approval for neoadjuvant therapy for early-stage NSCLC.
CheckMate 816
Efficacy of the combination was evaluated in CheckMate 816 (ClinicalTrials.gov identifier NCT02998528), a randomized, open-label trial in patients with resectable, histologically confirmed stage IB (≥ 4 cm), II, or IIIA NSCLC (American Joint Committee on Cancer/Union for International Cancer Control staging criteria) and measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1.). Patients were enrolled regardless of tumor PD-L1 status. A total of 358 patients were randomly assigned to receive either nivolumab plus platinum-doublet chemotherapy administered every 3 weeks for up to three cycles, or platinum-chemotherapy alone administered on the same schedule.
The main efficacy outcome measures were event-free survival and pathologic complete response by blinded independent central review. Median event-free survival 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) for those receiving chemotherapy alone. The hazard ratio was 0.63 (97.38% CI = 0.43–0.91, P = .0052). The pathologic complete response rate was 24% (95% CI = 18.0–31.0) in the nivolumab-plus-chemotherapy arm and 2.2% (95% CI = 0.6–5.6) in the chemotherapy-alone arm.
The most common adverse reactions (incidence ≥ 20%) occurring in patients treated with the combination were nausea, constipation, fatigue, decreased appetite, and rash. The addition of nivolumab to chemotherapy did not result in more frequent delays or cancellations of surgery. The median lengths of hospital stays following definitive surgery and the rates of adverse reactions identified as surgical complications were similar for patients in both arms of the trial.
The recommended nivolumab dose is 360 mg with platinum-doublet chemotherapy on the same day every 3 weeks for three cycles.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews may be ongoing at the other regulatory agencies.
This review also used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 5 months ahead of the FDA goal date; this application was also granted Priority Review.
