On March 4, 2022, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo®) with platinum-doublet chemotherapy for adult patients with resectable non-small cell lung cancer (NSCLC) in the neoadjuvant setting, representing the first FDA approval for neoadjuvant therapy for early-stage NSCLC.

FDA Approves Neoadjuvant Nivolumab and Platinum-Doublet Chemotherapy for Early-Stage Non-Small Cell Lung Cancer

Efficacy was evaluated in a randomized, open-label trial (CHECKMATE-816; NCT02998528) in patients with resectable, histologically confirmed stage IB (≥ 4 cm), II, or IIIA NSCLC using the American Joint Committee on Cancer and Union for International Cancer Control’s staging criteria and measurable disease using response evaluation criteria in solid tumors 1.1. Patients were enrolled regardless of tumor PD-L1 status. A total of 358 patients were randomized to receive either nivolumab plus platinum-doublet chemotherapy administered every three weeks for up to three cycles, or platinum-chemotherapy alone administered on the same schedule.

The main efficacy outcome measures were event-free survival (EFS) and pathologic complete response (pCR) by blinded independent central review. The median EFS was 31.6 months (95% CI = 30.2, not reached) in patients who received nivolumab plus chemotherapy 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 = 0.0052). The pCR 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 reported in 20% or more of patients were nausea, constipation, fatigue, decreased appetite, and rash. The addition of nivolumab to chemotherapy did not result in more frequent surgical delays or cancellations. 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.

The recommended nivolumab dose is 360 mg with platinum-doublet chemotherapy on the same day every three weeks for three cycles.

View the full prescribing information for nivolumab.

The review was conducted under Project Orbis, an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, 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.

The review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application five months ahead of FDA’s goal date.

FDA granted the application priority review. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.