Perioperative nivolumab (Opdivo) preserved health-related quality of life (HRQOL) and reduced the risk of deterioration compared with placebo in patients with resectable non-small cell lung cancer (NSCLC), according to long-term data from the phase 3 CheckMate 77T trial presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.
The exploratory analysis evaluated HRQOL using patient-reported outcome measures including the NSCLC-Symptom Assessment Questionnaire (NSCLC-SAQ) and the EQ-5D-3L visual analogue scale (VAS), achieving completion rates exceeding 90% across most evaluation time points.
Stage III N2 Disease Shows Significant Benefits
Patients with stage III N2 disease demonstrated particularly notable improvements with nivolumab treatment. The analysis showed those receiving nivolumab had a lower risk of HRQOL deterioration and delayed median time to definitive deterioration (TTDD) compared to placebo.
According to the NSCLC-SAQ instrument, the TTDD was 44.5 months in the nivolumab arm (n = 91) versus 31.4 months in the placebo arm (n = 90). The 12-, 24-, and 30-month TTDD rates in the respective arms were 88% and 69%, 77% and 55%, and 77% and 53%.
Using the EQ-5D-3L VAS instrument, the median TTDD was 44.5 months with nivolumab and 35.7 months with placebo. In the nivolumab arm, the TTDD rates at 12, 24, and 30 months were 81%, 77%, and 73%; in the placebo arm, these rates were 66%, 53%, and 53%.
The hazard ratios for deterioration in stage III N2 patients were 0.45 (95% CI, 0.26-0.79) based on NSCLC-SAQ total scores and 0.53 (95% CI, 0.31-0.92) for EQ-5D-3L VAS measurements.
Surgical Outcomes Analysis
Quality of life benefits were maintained across different surgical approaches. For patients who underwent simple lobectomy, the median TTDD was not reached in the nivolumab group (n = 58) versus 36.0 months in the placebo group (n = 49; HR, 0.41; 95% CI, 0.21-0.82) according to NSCLC-SAQ measurements.
By the EQ-5D-3L VAS instrument, patients receiving nivolumab who had a simple lobectomy experienced a median TTDD of 50.8 months versus 35.7 months with placebo (HR, 0.35; 95% CI, 0.17-0.69).
For patients achieving complete resection, the median TTDD was 44.5 months with nivolumab (n = 60) versus 36.0 months with placebo (n = 57; HR, 0.48; 95% CI, 0.24-0.93) based on NSCLC-SAQ scores.
Clinical Context and Significance
"What's important to note is that both in the N2 and non-N2 patients, if you look at departure of baseline QOL, other than the brief period after surgery, most patients remain within the nonclinically significant range, indicating that perioperative nivolumab did not harm these patients," said Jonathan D. Spicer, MD, PhD, medical director of the Thoracic Oncology Program at McGill University Health Centre. "In fact, it provided benefit in a significant majority of them, and this is durable throughout the course of observation."
The CheckMate 77T trial previously demonstrated that perioperative nivolumab led to a statistically significant and clinically meaningful event-free survival benefit versus placebo plus chemotherapy. The median event-free survival was not reached (95% CI, 28.9-not estimable) in the nivolumab arm versus 18.4 months (95% CI, 13.6-28.1) in the placebo arm (HR, 0.58; 95% CI, 0.43-0.78; P = .00025).
These data supported the October 2024 FDA approval of nivolumab with platinum-doublet chemotherapy as neoadjuvant treatment followed by nivolumab monotherapy after surgery as adjuvant treatment for adults with resectable NSCLC without EGFR mutations or ALK rearrangements.
Patient-Centered Outcomes Focus
The comprehensive approach to evaluating patient-reported outcomes represents a critical evolution in oncology research, shifting focus beyond traditional clinician-reported endpoints to embrace the patient's perspective. According to Dr. Spicer, maintaining a patient's quality of life through often-toxic cancer therapies remains an indispensable objective alongside prolonging survival.
The trial's findings demonstrate that nivolumab's immunomodulatory effects may mitigate symptom progression or treatment toxicity more effectively than chemotherapy alone, particularly in the vulnerable Stage III N2 population historically associated with poorer prognoses and increased treatment-related morbidity.
These results provide oncologists with robust evidence to advocate for nivolumab's inclusion in treatment protocols, especially for patients at high risk of recurrence, supporting the evolving standard of care paradigm that increasingly incorporates immunotherapy as a critical adjunct to surgery and chemotherapy.
