Perioperative versus neoadjuvant nivolumab for resectable NSCLC: a patient-level data analysis

New data from a landmark analysis, comparing results from CheckMate 816 and CheckMate 77T, report a decreased risk of disease recurrence or death in patients with resectable NSCLC who received perioperative nivolumab plus chemotherapy and surgery compared to those who received only neoadjuvant nivolumab plus chemotherapy.

Previously, the CheckMate 816 study reported significant improvements in event-free survival (EFS) and pathological complete response (pCR) with neoadjuvant nivolumab plus chemotherapy in patients with resectable non-small cell lung cancer (NSCLC).  Nivolumab plus chemotherapy is the sole approved neoadjuvant-only immunotherapy-containing regimen and the standard of care neoadjuvant treatment for eligible patients with resectable NSCLC. The CheckMate 77T built further on this treatment regimen and demonstrated clinically meaningful improvements in EFS and pCR with perioperative nivolumab vs. placebo. At WCLC 2024, the first individual patient-level data analysis of CheckMate 77T and CheckMate 816 to evaluate the contribution of the adjuvant phase of the perioperative nivolumab treatment regimen were presented.

Study design

This analysis included patients in CheckMate 77T who received neoadjuvant nivolumab plus chemotherapy, followed by definitive surgery and ≥1 dose of adjuvant nivolumab and compared them to patients in CheckMate 816 who received neoadjuvant nivolumab plus chemotherapy followed by definitive surgery. Inverse probability of treatment weighting (IPTW) was applied to adjust for potential cross-trial imbalances of baseline covariates using propensity score weights (stabilised average treatment effect for the treated [ATT] and stabilised average treatment effect [ATE]).

Results

In total, 139 patients were included in the perioperative nivolumab group and 147 patients were included in the neoadjuvant nivolumab group. Median follow-up was 29.5 months for CheckMate 816 and 33.3 months for CheckMate 77T. After weighting, baseline characteristics were well balanced between both groups. Perioperative nivolumab demonstrated an EFS benefit from time of surgery vs. neoadjuvant nivolumab (HR[95% CI]: unweighted, 0.59[0.38-0.92]; weighted [ATT], 0.56[0.35-0.90]; weighted [ATE], 0.61[0.39-0.97]).

Landmark EFS benefit was also observed with perioperative vs. neoadjuvant nivolumab in patients with PD-L1 <1% (HR[95%CI]: 0.51[0.28-0.93]) or ≥1% (HR[95%CI]: 0.86[0.44-1.70]) and across clinical stages (IB/II: HR[95%CI]: 0.53[0.25-1.11] and III: HR[95%CI]: 0.63[0.37-1.07])). Additionally, landmark EFS favoured perioperative nivolumab in patients with (HR[95%CI]: 058[0.14-2.40]) or without pCR (HR[95%CI]: 0.65[0.40-1.06]). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 27% of patients treated with perioperative nivolumab and in 35% of those who received neoadjuvant nivolumab. TRAEs of grade 3-4 leading to treatment discontinuation were reported in respectively 6% and 5% of patients treated with perioperative and neoadjuvant nivolumab.

Conclusions

In the absence of a randomised-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 two randomised phase III trials. Perioperative nivolumab showed EFS improvement vs. neoadjuvant nivolumab in patients with resectable NSCLC, including those with PD-L1 <1% or without pCR. Given the limitations of propensity score weighted analysis, these results should be interpreted with caution.

Reference

Forde P, et al. Perioperative vs Neoadjuvant Nivolumab for Resectable NSCLC: Patient-Level Data Analysis of CheckMate 77T vs CheckMate 816. Presented at WCLC 2024; Abstract 3589.