Surgical and pathologic efficacy of neoadjuvant immunochemotherapy in EGFR-mutant non-small cell lung cancer

Neoadjuvant immunochemotherapy (neo-ICT) has demonstrated promising pathological response for resectable non-small cell lung cancer (NSCLC), while its role in epidermal growth factor receptor (EGFR)-mutated NSCLC remains unclear. Here, we aim to explore whether patients with EGFR-sensitive mutation and positive programmed cell death ligand 1 (PD-L1) expression may benefit from it.

We retrospectively reviewed 15 patients with stage IIB-IIIC EGFR-mutant NSCLC and a PD-L1 tumor proportion score (TPS) of ≥10%, who received neo-ICT (with or without bevacizumab) followed by surgery at The First Affiliated Hospital of Guangzhou Medical University between 2020 and 2026. The primary endpoints were pathological complete response (pCR) and major pathological response (MPR), and the secondary endpoints included R0 resection rate, tumor and nodal downstaging rates, event-free survival (EFS), and safety.

All patients underwent minimally invasive thoracoscopic surgery with 100% R0 resection. The MPR rate (including pCR) was 33% (5/15), of which 13% (2/15) achieved pCR and 20% (3/15) achieved non-pCR MPR. Pathologic downstaging was achieved in 67% of patients, and nodal downstaging in 73%. With a median follow-up of 29.8 months, the median EFS was 30.1 months [95% confidence interval (CI): 22.5-not reached], the 12-month EFS rate was 93.3% (95% CI: 81.5-100.0%), and the 24-month EFS rate was 66.7%. Neoadjuvant therapy was well tolerated, with no grade 3 or higher treatment-related adverse events, no surgical delays, and no treatment-related deaths reported.

Among patients with PD-L1-positive EGFR-mutant NSCLC, neo-ICT yielded pathological and surgical responses with acceptable safety in this small retrospective cohort. Observed pathological benefits remain exploratory, and prospective studies are required to validate its clinical utility before defining its role as a neoadjuvant regimen for this patient subgroup.