KEY TAKEAWAYS
- Phase 2 trial CheckMate-816 evaluated neoadjuvant treatment for resectable non-small-cell lung cancer (NSCLC).
- The trial’s primary aim was to evaluate event-free survival per medical standards.
- The trial allocated 358 patients to receive either nivolumab plus platinum-doublet or platinum-doublet chemotherapy alone before surgical removal.
- The nivolumab plus chemotherapy group demonstrated a statistically significant and clinically meaningful enhancement in EFS compared to the chemotherapy-only group.
- The hazard ratio for overall survival was 0.57, indicating no harm in overall survival or adverse effect on patients’ receipt and timing of surgery or surgical outcomes.
- The US FDA approved the neoadjuvant resectable NSCLC treatment using nivolumab combined with platinum-doublet chemotherapy.
The neoadjuvant treatment of patients with resectable non-small-cell lung cancer (NSCLC) was approved by the US Food and Drug Administration (FDA) on March 4, 2022, utilizing nivolumab in combination with platinum-doublet chemotherapy. We will discuss the FDA’s evaluation of the critical clinical data and regulatory factors underpinning this approval. The endorsement was founded on the outcomes of CheckMate-816. This worldwide, multiregional, active-controlled clinical study arbitrarily allocated 358 patients with operable non-small cell lung cancer, stage IB (≥4 cm) to IIIA (N2) according to the American Joint Committee on Cancer seventh staging edition, to obtain either nivolumab plus platinum-doublet or platinum-doublet chemotherapy alone for three cycles before intended surgical removal. Per medical standards, the primary efficacy endpoint substantiating this approval was event-free survival (EFS).
During the initial scheduled interim analysis, the hazard ratio (HR) for event-free survival (EFS) was 0.63 (95% CI, 0.45 to 0.87; P = .0052; statistical significance boundary = .0262) in favor of the nivolumab plus chemotherapy group. The median EFS was 31.6 months (95% CI, 30.2 to not reached) in the nivolumab plus chemotherapy group compared to 20.8 months (95% CI, 14.0 to 26.7) in the chemotherapy-only group. At the time of a pre-specified interim analysis for overall survival, 26% of the patients had decreased. The hazard ratio for overall survival was 0.57 (95% confidence interval, 0.38 to 0.87; P = .0079; statistical significance boundary = .0033). In the nivolumab-containing arm, 83% of patients underwent definitive surgery; in the chemotherapy-only arm, 75% underwent the same procedure. The endorsement, which marks the initial approval for any neoadjuvant treatment regimen for non-small cell lung cancer (NSCLC) in the United States, was substantiated by a statistically significant and clinically meaningful enhancement in event-free survival (EFS) without any indication of harm in overall survival (OS) or adverse effect on patients’ receipt and timing of surgery or surgical outcomes.
Source:https://pubmed.ncbi.nlm.nih.gov/37141544/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02998528
Akinboro O, Drezner N, Amatya A, Runyan J, Fourie-Zirkelbach J, Zhao M, Bi Y, Korsah K, Mixter B, Tang S, Larkins E, Pazdur R, Beaver JA, Singh H. US Food and Drug Administration Approval Summary: Nivolumab Plus Platinum-Doublet Chemotherapy for the Neoadjuvant Treatment of Patients With Resectable Non-Small-Cell Lung Cancer. J Clin Oncol. 2023 May 4:JCO2202509. doi: 10.1200/JCO.22.02509. Epub ahead of print. PMID: 37141544.
