Exploratory Data Support Perioperative Nivolumab for NSCLC

SAN DIEGO — An analysis comparing patient-level data from two recent phase 3 trials demonstrated an approximately 40% reduction in the risk for non–small cell lung cancer (NSCLC) recurrence or death after surgery in those who receive perioperative nivolumab and chemotherapy vs nivolumab and chemotherapy in the neoadjuvant setting only.

These findings support the use of both neoadjuvant and adjuvant nivolumab in patients with resectable NSCLC, Patrick M. Forde, MD, reported at the World Conference on Lung Cancer (WCLC) 2024.

Although an exploratory analysis, these results may help inform our day-to-day clinical decisions when we see patients who have received neoadjuvant therapy and surgery for resectable lung cancer, said Forde, director of the Thoracic Oncology Clinical Research Program at Johns Hopkins University, Baltimore.

Currently, neoadjuvant nivolumab plus chemotherapy is the sole approved guideline-recommended neoadjuvant immunotherapy–containing treatment for eligible patients with resectable lung cancer, but the CheckMate 77T trial recently revealed that the perioperative approach led to a significant and clinically meaningful event-free survival (EFS) benefit in this population.

Still, there have been no head-to-head comparisons of the neoadjuvant and perioperative strategies.

In the new analysis, Forde and his colleagues conducted an exploratory analysis to attempt to compare these approaches. The researchers compared individual patient-level data from CheckMate 77T participants who received neoadjuvant nivolumab followed by surgery and at least one dose of adjuvant nivolumab with data from CheckMate 816 participants who received neoadjuvant-only nivolumab and chemotherapy followed by surgery.

The CheckMate 816 trial showed an EFS benefit with neoadjuvant nivolumab plus chemotherapy vs chemotherapy alone (hazard ratio [HR], 0.63), while CheckMate 77T demonstrated a significant EFS benefit from perioperative nivolumab vs placebo (HR, 0.58).

Pathologic complete response rates were “quite similar” across the two trials at 24%-25%, noted Forde, who is also co-director of the Division of Upper Aerodigestive Malignancies at Johns Hopkins University.

After performing an exploratory propensity score weighting analysis to allow for a simplified reproduction of a randomized trial, Forde and colleagues found an EFS benefit from the time of surgery with perioperative nivolumab, both in weighted and unweighted analyses (HRs, 0.56 and 0.59, respectively).

Among patients with or without pathologic complete response, the EFS benefit trended in favor of the perioperative approach (HR, 0.58; 95% CI, 0.14-2.40) vs neoadjuvant-only approach (HR, 0.65; 95% CI, 0.40-1.06), though neither finding was statistically significant.

A particular EFS benefit was seen with perioperative nivolumab in patients without programmed death-ligand 1 (PD-L1) expression (HR, 0.51) vs with PD-L1 expression (HR, 0.86).

Although both curves trended in favor of perioperative therapy, PD-L1–positive tumors are known to benefit from either neoadjuvant or perioperative or adjuvant therapy, so it is possible that longer follow-up is needed in this subgroup, Forde said.

A similar EFS benefit for perioperative nivolumab was also seen across clinical disease stages IB and II and clinical stage III.

Safety was also similar across the analysis populations, Forde noted.

The results support the use of perioperative nivolumab as an option for eligible patients with resectable NSCLC, Forde concluded.

Invited discussant Nan Wu, MD, of Peking University Cancer Hospital and Institute, Beijing, China, noted, however, that more validation of the findings is needed, as well as more clarity regarding potential markers to identify patients most likely to benefit from perioperative or neoadjuvant nivolumab.

But, Forde noted, without a randomized controlled clinical trial available to us, this analysis “represents the only comparison of perioperative vs neoadjuvant-only immunotherapy treatment for patients with resectable lung cancer.”

Wu had no disclosures. Forde reported receiving grants or contracts from AstraZeneca, Bristol Myers Squibb, Novartis, Regeneron, and BioNTech and consulting fees from Ascendis, AstraZeneca, Bristol Myers Squibb, CureVac, Novartis, Regeneron, and others.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on X: @SW_MedReporter.