Patient-Level Data Support Perioperative Nivolumab Use in Resectable NSCLC

Perioperative treatment with nivolumab (Opdivo) demonstrated an approximate 40% reduction in risk of disease recurrence or death after surgery compared with neoadjuvant nivolumab plus chemotherapy among patients with resectable non-small cell lung cancer (NSCLC), according to a patient-level data analysis of the phase 3 CheckMate 77T trial (NCT04025879) vs the phase 3 CheckMate 816 trial (NCT02998528).

As a result, the analysis may help to inform of the potential benefit of adjuvant nivolumab following neoadjuvant nivolumab plus chemotherapy treatment and surgery, further supporting its use in eligible patients, Patrick Forde, MBBCH, noted in his presentation at the 2024 IASLC World Conference on Lung Cancer.¹ Forde is codirector of the Division of Upper Aerodigestive Malignancies and director of the Thoracic Oncology Clinical Research Program at Johns Hopkins Medicine in Baltimore Maryland.

At median follow-ups of 29.5 months and 33.3 months in the CheckMate 816 and CheckMate 77T trials, respectively, the landmark event-free survival (EFS) via blinded independent central review (BICR) showed added benefit in the weighted average treatment effect (HR, 0.61; 95% CI, 0.39-0.97) for patients who received perioperative nivolumab (n = 139) compared with patients who received neoadjuvant nivolumab plus chemotherapy (n = 147).

“When we performed an unweighted analysis of all patients who had surgery, and irrespective of whether they received neoadjuvant nivolumab in the CheckMate 77T trial, that adds to all of the trends in favor of perioperative therapy,” Forde explained.

When stratifying landmark EFS based on pathologic complete response (pCR), those with (40.7% [HR, 0.58; 95% CI, 0.14-2.40]), vs without (30.5% [HR, 0.65; 95% CI, 0.40-1.06]), showed more favorable reduction in the risk for EFS with perioperative nivolumab, compared with neoadjuvant nivolumab plus chemotherapy.

Similarly, stratification by tumor PD-L1 expression also demonstrated improved HRs, regardless of status. For patients with PD-L1 status of less than 1% (HR, 0.51; 95% CI, 0.28-0.93), compared with those of 1% or more (HR, 0.86; 95% CI, 0.44-1.70) perioperative nivolumab further reduced the risk for disease recurrence or death, compared with neoadjuvant nivolumab plus chemotherapy.

Lastly, stratification by clinical stage also demonstrated improved EFS outcomes with perioperative nivolumab vs neoadjuvant nivolumab plus chemotherapy, regardless of tumor stage: The HR among those with stage IB to II disease was 0.53 (95% CI, 0.25-1.11), compared with 0.63 (95% CI, 0.37-1.07) in patients with stage III NSCLC.

According to Forde, perioperative nivolumab had a generally manageable safety profile. Treatment-related adverse events (TRAEs) of any grade leading to discontinuation occurred in 16% of the perioperative treatment group, compared with 11% in the neoadjuvant setting. Further, surgery-related AEs occurred in 38% vs 42%, respectively.

In the analysis, those who were included were either enrolled in the CheckMate 77T trial (neoadjuvant nivolumab plus chemotherapy followed by definitive surgery and at least 1 or more doses of adjuvant nivolumab) or the CheckMate 816 trial (neoadjuvant nivolumab plus chemotherapy followed by definitive surgery).

The primary endpoint was EFS by BCIR landmarked from time of surgery.

“In the absence of a randomized-controlled trial, this analysis represents the only comparison of perioperative vs neoadjuvant-only immunotherapy treatments for patients with resectable NSCLC, using individual patient-level data from 2 randomized phase 3 trials,” Forde noted.

Reference

1. Forde P, Peters S, Donington J, et al. Perioperative vs Neoadjuvant Nivolumab for Resectable NSCLC: Patient-Level Data Analysis of CheckMate 77T vs CheckMate 816. Presented at: 2024 IASLC World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract PL02.08.