Individual participant data meta-analysis comparing neoadjuvant to perioperative chemoimmunotherapy in early-stage non-small cell lung cancer according to PD-L1 status.

e20035 Background: Neoadjuvant and perioperative chemo-immunotherapy are two standard-of-care treatment options for patients with early-stage Non-Small Cell Lung Cancer, both of which improve event-free-survival (EFS). A recent reconstructed individual patient data (IPD) meta-analysis found no difference in EFS between these approaches. However, another patient-level analysis of CheckMate trails 816 and 77T reported that perioperative nivolumab significantly improves EFS, particularly in the PD-L1 negative subgroup. Our study aims to compare neoadjuvant and peri-operative chemo-immunotherapy based on PD-L1 status using reconstructed IPD. Methods: Data were collected from Kaplan-Meier curves of eight randomized trials, including five perioperative and three neoadjuvant trials. Only trials with Kaplan-Meier curves stratified by PD-L1 levels were included. Data extraction, IPD reconstruction, and survival analyses were conducted using the IPDfromKM tool. Patients were stratified according to their PD-L1 tumor proportion score (TPS) as negative (≤1%), positive (1-49%) and high (≥50%). Statistical comparison of EFS between the perioperative and neoadjuvant arms were performed across these subgroups. Results: A total of 1656 participants were included in our analysis with 1420 patients in the perioperative arm and 236 in the neoadjuvant arm. A total of 447 EFS events were analyzed. The PD-L1 subgroups included 293 patients with negative PD-L1 (≤1%), 269 with positive PD-L1, (1-49%), and 192 with high PD-L1 (≥50%). No significant differences in EFS were observed between perioperative and neoadjuvant approaches among patients with any PD-L1 TPS (P=0.634) or within any PD-L1 subgroup (negative: P=0.449; positive: P=0.311; high: P=0.334). Conclusions: This reconstructed IPD meta-analysis found no significant difference in EFS between perioperative and neoadjuvant chemo-immunotherapy in ES-NSCLC, regardless of PD-L1 status. Treatment decisions should consider other patient-specific factors beyond PD-L1 status. Larger randomized trials are needed to further identify patients who may benefit from additional immunotherapy after surgery. Event-free survival (EFS) by PDL-L1 TPS subgroup. PD-L1 Subgroup Perioperative EFS (months) Neoadjuvant EFS (months) P-value All Patients Not Reached 31.74 0.634 PD-L1 ≤1% 26.87 25.04 0.449 PD-L1 1-49% Not Reached Not Reached 0.311 PD-L1 ≥50% Not Reached Not Reached 0.334