Perioperative Nivolumab Shows Long-Term EFS, Favorable OS in Resectable NSCLC

Perioperative nivolumab (Opdivo; Bristol Myers Squibb) continued to show long-term event-free survival (EFS) benefit and a favorable overall survival (OS) benefit compared with placebo in patients with resectable non–small cell lung cancer (NSCLC), with no novel safety signals observed, according to results from the first prespecified interim analysis of the phase 3 CheckMate 77T study (NCT04025879), published by investigators in the Journal of Clinical Oncology and presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.^1,2

Image Credit: © David A Litman - stock.adobe.com

CheckMate 77T Demonstrated Improved Survival With Nivolumab

CheckMate 77T, a randomized, double-blind trial, assigned adults with resectable stage IIA to IIIB NSCLC to receive either neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo every 3 weeks for 4 cycles, followed by surgery and adjuvant nivolumab or placebo every 4 weeks for 1 year. Investigators sought to determine EFS, according to a blinded independent review.³

Following a median follow-up period of 25.4 months, 70.2% of patients reached 18-month EFS in the nivolumab group, compared with 50.0% in the chemotherapy group (hazard ratio [HR]: 0.58 [97.36% CI, 0.42—0.81; P < .001). Pathological complete response (pCR) rate, a key secondary end point, was also significantly higher among patients in the nivolumab group (25.3%) compared with chemotherapy (4.7%; odds ratio: 6.64 [95% CI, 3.40—12.97]).³

Prespecified Interim Analysis Shows Sustained EFS

For this prespecified interim analysis, investigators extended the median follow-up period (41.0 months) to further elucidate the long-term EFS and OS effects of perioperative nivolumab vs placebo. They also aimed to conduct an exploratory biomarker analysis to determine in which patients EFS was most prolific.¹

According to the authors, nivolumab sustained EFS benefit vs placebo at the longer follow-up point (HR: 0.61 [95% CI, 0.46—0.80]; 30-month EFS rates, 61% versus 43%) among all randomized patients and regardless of programmed death-ligand 1 (PD-L1) expression, tumor histology, or disease stage. Furthermore, EFS from surgery was found to favor nivolumab compared with placebo in patients with pCR (HR: 0.90 [95% CI, 0.19—4.15]) or without (HR: 0.72 [95% CI, 0.50—1.05]).¹

Among biomarker-evaluable patients (nivolumab, n = 98; placebo, n = 92), those with circulating tumor DNA (ctDNA) clearance with or without pCR had improved EFS compared with patients without clearance or pCR. Additionally, EFS was favored in patients with tumor genomic alterations—including KRAS, STK1, or KEAP1 mutations—treated with nivolumab compared with placebo. Regardless of mutation status, higher ctDNA clearance and pCR rates were observed in patients treated with nivolumab vs placebo, the investigators found.¹

Interim analysis of OS was also conducted. The investigators found that nivolumab showed a trend of OS improvement vs placebo among all randomized patients (HR: 0.85; [97.63% CI, 0.58—1.25]; median OS: not reached in both arms; 30-month OS rates, 78% vs 72%, respectively). These data indicate that OS remained improved with nivolumab, even throughout a longer follow-up period.¹

Nivolumab is a fully human antibody against PD-1, and in combination with platinum-doublet chemotherapy, it has become a standard neoadjuvant treatment for eligible patients with resectable NSCLC. Perioperative treatment with nivolumab can further reduce the risk of relapse, which is a major obstacle for patients with NSCLC. Pharmacists and primary care providers should ensure they evaluate patients on their feasibility for perioperative treatment and monitor their response throughout nivolumab administration for possible adverse effects.^1,3

REFERENCES

1. Cascone T, Award MM, Spicer J, et al. Perioperative nivolumab (NIVO) vs placebo (PBO) in patients (pts) with resectable NSCLC: Updated survival and biomarker analyses from CheckMate 77T. J Clin Oncol. 2025;43(17). doi:10.1200/JCO.2025.43.17_suppl.LBA8010

2. A Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Removal and Adjuvant Treatment With Nivolumab or Placebo for Participants With Surgically Removable Early Stage Non-small Cell Lung Cancer. National Library of Medicine. ClinicalTrials.gov Identifier: NCT04025879. Last Updated July 23, 2024. Accessed June 11, 2025. https://clinicaltrials.gov/study/NCT04025879

3. Cascone T, Award MM, Spicer JD, et al. Perioperative nivolumab in resectable lung cancer. N Engl J Med. 2024;390(19):1756-1769. doi:10.1056/NEJMoa2311926