Perioperative Nivolumab Improves EFS in Resectable NSCLC

Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non-small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.

In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the European Society for Medical Oncology (EMSO) 2023 Congress in Madrid.

"CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non-small cell lung cancer," said Cascone, associate professor in the Division of Cancer Medicine at University of Texas MD Anderson Cancer Center, Houston.

Invited discussant Marina Garassino, MBBS, professor of medicine and director of the Thoracic Oncology Program at the University of Chicago, noted that the "practice-changing" CheckMate 77T findings — including the "highly statistically significant impressive hazard ratio of 0.58" — add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.

This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck's pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.

The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.

Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7–44.2 months (not reached vs 18.4 months; HR, 0.58; P = .00025).

The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs stage III disease (HR, 0.81 vs 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs 1% or greater (HR, 0.73 vs 0.52).

Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs 4.7%; odds ratio [OR], 6.64) and major pathological response (35.4% vs 12.1%; OR, 4.01) — the trial's secondary endpoints.

In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Cascone added.

No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.

Despite the promising findings, some questions remain, said Garassino.

First, should PD-L1-negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.

So, "the answer is yes, we should treat" these patients, she said.

But a big question is whether patients who don't achieve a pathological complete response need adjuvant therapy. "We really don't know," she continued. "What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don't achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low."

CheckMate 77T is funded by Bristol-Myers Squibb. Cascone and Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.

European Society for Medical Oncology 2023 Congress: Abstract LBA1. Presented October 21, 2023.

Ann Oncol. Published online October 21, 2023. Abstract

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, 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 sworcester@mdedge.com or on Twitter: @SW_MedReporter.

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Cite this: Perioperative Nivolumab Improves EFS in Resectable NSCLC - Medscape - Oct 21, 2023.