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FDA approves perioperative and post-surgical adjuvant nivolumab for resectable non-small cell lung cancer

On October 3rd 2024, the U.S. Food and Drug Administration (FDA) recent approved nivolumab as a perioperative therapy for patients with resectable stage IIA to IIIB non-small cell lung cancer (NSCLC).1 NSCLC, a historically challenging disease with limited treatment options beyond surgery in resectable cases, has seen a paradigm shift with the emergence of immunotherapy. Nivolumab, a PD-1 inhibitor, has proven its capacity to harness the immune system against cancer cells, positioning it as a critical asset in this setting.

The regimen was assessed in the Phase III, randomized CheckMate 77T trial (NCT04025879), which randomly assigned 461 patients 1:1 to either receive perioperative nivolumab or placebo every 3 weeks for up to 4 cycles, followed by adjuvant treatment with either continued single-agent nivolumab or placebo every 4 weeks for up to 13 cycles. The primary outcome was event-free survival (EFS) according to blinded independent review. Secondary outcomes included pathological complete response and major pathological response, overall survival, and safety.

Perioperative treatment with nivolumab plus chemotherapy significantly improved event-free survival (EFS) in resectable NSCLC. At 25.4 months follow-up, 18-month EFS was 70.2% versus 50.0% in patients receiving nivolumab or chemotherapy respectively (HR 0.58; 97.36% CI, 0.42–0.81; P<0.001). Pathological complete response was higher in the nivolumab arm (25.3% vs. 4.7%; OR 6.64) as was major pathological response (35.4% vs. 12.1%; OR 4.01). Grade 3-4 treatment-related adverse events occurred in 32.5% and 25.2% of patients receiving nivolumab and chemotherapy respectively.2

At another follow-up of 33.3 months, 2-year EFS rates further show the superiority of nivolumab over chemotherapy (65% vs. 44%; HR 0.59). Higher circulating tumor DNA (ctDNA) clearance (66% vs. 38%) and lower ctDNA recurrence (8% vs. 20%) were additionally observed in the nivolumab arm.3

This dual-purpose approach, integrating both preoperative and postoperative therapy, highlights the efficacy of nivolumab in addressing minimal residual disease that often contributes to recurrence in patients with NSCLC. It also reflects a broader shift toward perioperative immunotherapies across various cancers, reinforcing the potential of these treatments to redefine long-term management and improve outcomes for patients with resectable tumors.

References:

  1. Center for Drug Evaluation and Research. FDA approves neoadjuvant/adjuvant nivolumab for resectable NSCLC [Internet]. FDA; [cited 2024 Nov 7]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-nivolumab-resectable-non-small-cell-lung-cancer
  2. Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, et al. Perioperative nivolumab in Resectable Lung Cancer. New England Journal of Medicine. 2024 May 16;390(19):1756–69. doi:10.1056/nejmoa2311926
  3. Provencio Pulla M, Awad M, Cascone T, Spicer JD, He J, Lu S, et al. LBA50 perioperative nivolumab (NIVO) v placebo (PBO) in patients (PTS) with RESECTABLE NSCLC: Clinical Update from the phase III checkmate 77T study. Annals of Oncology. 2024 Sept;35. doi:10.1016/j.annonc.2024.08.2291