Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.

Abstract

BACKGROUND:

Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.

METHODS:

In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.

RESULTS:

The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.

CONCLUSIONS:

In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

• Authors: Patrick M Forde, Jonathan Spicer, Shun Lu, Mariano Provencio, Tetsuya Mitsudomi, Mark M Awad, Enriqueta Felip, Stephen R Broderick, Julie R Brahmer, Scott J Swanson, Keith Kerr, Changli Wang, Tudor-Eliade Ciuleanu, Gene B Saylors, Fumihiro Tanaka, Hiroyuki Ito, Ke-Neng Chen, Moishe Liberman, Everett E Vokes, Janis M Taube, Cecile Dorange, Junliang Cai, Joseph Fiore, Anthony Jarkowski, David Balli, Mark Sausen, Dimple Pandya, Christophe Y Calvet, Nicolas Girard, CheckMate 816 Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 386 Issue 21 Pg. 1973-1985 (05 26 2022) ISSN: 1533-4406 [Electronic] United States
• PMID: 35403841 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2022 Massachusetts Medical Society.

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Immunological
• Ipilimumab
• Platinum Compounds
• Nivolumab

Topics

• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Agents, Immunological (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, surgery)
• Humans
• Ipilimumab (adverse effects)
• Lung Neoplasms (drug therapy, surgery)
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (drug therapy)
• Nivolumab (adverse effects, therapeutic use)
• Platinum Compounds (adverse effects, therapeutic use)