On October 3, 2024, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo®) with platinum-doublet chemotherapy as neoadjuvant treatment, followed by single-agent nivolumab after surgery as adjuvant treatment, for adults with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) variants or anaplastic lymphoma kinase (ALK) rearrangements.
Efficacy was evaluated in CHECKMATE-77T (NCT04025879), a randomized, double-blind, placebo-controlled multicenter trial in 461 patients with previously untreated and resectable NSCLC (stage IIA to select stage IIIB, according to AJCC 8th edition). Patients were randomized 1:1 to receive either nivolumab or placebo, with platinum-based chemotherapy, every three weeks for up to 4 cycles (neoadjuvant treatment) followed by either continued single-agent nivolumab or placebo every four weeks for up to 13 cycles (adjuvant treatment).
The major efficacy outcome measure was event-free survival (EFS) as assessed by blinded independent central review. Median EFS was not reached (95% CI = 28.9, not estimable) in the nivolumab arm and 18.4 months (95% CI = 13.6, 28.1) in the chemotherapy arm (hazard ratio = 0.58 [95% CI = 0.43, 0.78]; p = 0.00025). At the prespecified interim analysis, overall survival was not formally tested for statistical significance; however, a descriptive analysis revealed no detriment.
Adverse reactions were similar to those occurring in other clinical trials of nivolumab with chemotherapy. Of those who received neoadjuvant nivolumab, 5.3% were unable to undergo surgery because of adverse reactions compared with 3.5% in the placebo arm. In addition, 4.5% who received neoadjuvant treatment and surgery in the nivolumab arm had delays in surgery because of adverse reactions compared with 3.9% in the placebo arm. See the prescribing information on Drugs@FDA for additional safety information.
The recommended nivolumab dosage is 360 mg every three weeks (neoadjuvant treatment) and 480 mg every four weeks (adjuvant treatment). Nivolumab should be administered prior to chemotherapy when administered on the same day. View the full prescribing information for nivolumab on Drugs@FDA.
The FDA conducted the review under Project Orbis, an Oncology Center of Excellence (OCE) initiative that provides a framework for concurrent submission and review of oncology drugs among international partners. For its review, the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Israel’s Ministry of Health. The application reviews are ongoing at the other regulatory agencies. The applicant used the Assessment Aid to facilitate the FDA’s review.
Healthcare professionals should report all serious adverse events suspected to be 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 applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.