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Perioperative nivolumab not only extends event-free survival (EFS) but also does not compromise quality of life in patients with resectable non-small cell lung cancer (NSCLC), including those with high-risk advanced stage III N2 disease, according to an exploratory analysis from CheckMate 77T.

Patient-reported outcomes (PRO) data revealed that, among patients with stage III N2 disease, neoadjuvant nivolumab plus chemotherapy followed by adjuvant nivolumab reduced the risk of health-related quality of life (HRQoL) deterioration by about 50% compared to neoadjuvant chemotherapy alone. These benefits also extended to patients undergoing more extensive surgeries.

"Maintaining quality of life during and after treatment is vital to long-term success," explained lead investigator Jonathan Spicer, MD, who presented the data at the World Conference on Lung Cancer (WCLC) 2025 in Barcelona, Spain. "These results show that perioperative nivolumab supports both survival and patient well-being," Spicer, of McGill University Health Centre, Montreal, Canada, said in a statement. 

No Hit to QoL

The treatment landscape for resectable NSCLC has "changed dramatically over the last few years with the introduction of neoadjuvant and perioperative regimens," Spicer explained during a press briefing.

In the phase 3 CheckMate 77T study, adults with resectable stage IIA to IIIB NSCLC were randomized to neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo, followed by surgery and adjuvant nivolumab or placebo. Interim findings, published in 2023, revealed that perioperative nivolumab led to a significant EFS and pathologic complete response benefit compared to neoadjuvant chemotherapy alone. In the overall population of 461 patients, 18-month EFS was significantly higher in the perioperative nivolumab group vs the chemotherapy group — 70.2% vs 50.0% (hazard ratio [HR], 0.58). 

Among the 181 patients with clinical stage III N2 NSCLC, the EFS benefit was also significant. Median EFS was 30.2 months in the perioperative nivolumab group vs 10 months in the placebo group (HR, 0.46). Significantly more patients in the perioperative nivolumab group achieved a pathologic complete response — 22% vs 5.6% (HR, 0.60).

To assess HRQoL in patients with stage III N2 or non-N2 disease, the researchers relied on PRO data from two widely used instruments that measure symptom burden and overall health status: the NSCLC-Symptom Assessment Questionnaire (NSCLC-SAQ) and the European Quality of Life 5 Dimensions (EQ-5D-3L) visual analogue scale (VAS).

More than 90% of patients in both treatment arms completed PRO assessments across most timepoints.

Overall, perioperative nivolumab did not negatively impact HRQoL compared with placebo. Regardless of nodal status, baseline HRQoL scores were "generally maintained" through long-term follow-up, outside of the expected temporary declines at the post-surgical and pre-adjuvant visit, Spicer explained. 

Notably, patients with stage III N2 NSCLC had a significantly lower risk for HRQoL deterioration and delayed time to definitive deterioration with perioperative nivolumab vs placebo — a 55% lower risk based on the NSCLC-SAQ (HR, 0.45) and a 47% lower risk on the EQ-5D-3L VAS (HR, 0.53) — with no difference in patients who underwent single lobectomy or complete tumor resection. Based on NSCLC-SAQ findings, for instance, perioperative nivolumab was associated with similar reductions in the risk of HRQoL deterioration in patients who had single lobectomy (HR, 0.41) and complete tumor resection (HR, 0.48).

Patients with stage III non-N2 disease demonstrated a numerically lower risk for HRQoL deterioration but the differences were not significant, Spicer reported.

Overall, Spicer said, the long-term PRO data from CheckMate 77T showed that the survival gains with perioperative nivolumab are not achieved at the expense of quality of life. Instead, patients treated with nivolumab maintained stable symptom control and health status over time, including those with stage III N2 disease.

Balancing Quantity With Quality: It's Personal

Speaking at the briefing, patient research advocate Merel Hennink applauded the PRO study of nivolumab and emphasized the need for more PROs, not only within the studies, but also in clinical practice, "so that we can really have an informed decision if we have to choose a new treatment option."

Hennink was diagnosed in November 2014 with stage IV ROS1+ lung cancer, a rare oncogene-driven subtype affecting fewer than 1% of lung cancer patients. She embarked on a journey of targeted therapy beginning with crizotinib in March 2015, followed by lorlatinib since 2016.

With any new drug, "the first thing that we always look at is efficacy. What is the overall survival? What is progression-free survival?" Hennink said. 

Then comes side effects, which are often described as "manageable. But what is manageable? Is it according to an a priori theory or is it according to what patients really think?" she wondered. 

From the patient's point of view, "we only can choose our next line of treatment if we really know how the side effects impact the patient's life and their quality of life because the balance between quantity and quality is personal, and it's not this is the best treatment because the overall survival is the best."

The study was supported by Bristol Myers Squibb. Spicer had no relevant disclosures. Hennink serves on the executive board of Lung Cancer Europe.