Improved Event-Free Survival after Complete or Major Pathologic Response in Patients with Resectable NSCLC Treated with Neoadjuvant Chemoimmunotherapy Regardless of Adjuvant Treatment: a Systematic Review and Individual Patient Data Meta-Analysis

INTRODUCTION:Neoadjuvant chemoimmunotherapy has reshaped the treatment landscape for resectable NSCLC, yet the prognostic significance of pathologic response remains unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis to evaluate the impact of achieving pathologic complete response (pCR) or major pathologic response (MPR) on event-free survival (EFS) and assessed the influence of adjuvant immunotherapy. METHODS:We performed an IPD meta-analysis of prospective clinical trials on neoadjuvant or perioperative anti-programmed death-ligand 1 in combination with platinum-based chemotherapy in patients with resectable NSCLC. The IPD was extracted from Kaplan-Meier curves for pCR and MPR from the included studies. Survival outcomes were compared between patients achieving pCR or MPR and those who did not, considering both intention-to-treat and resected populations. RESULTS:Achieving pCR or MPR was associated with improved EFS in the intention-to-treat population (pCR, hazard ratio = 0.13; MPR, hazard ratio = 0.18, respectively) with a 24 months EFS rate of 94% and 88% for patients who achieved pCR and MPR, respectively. Independently from pCR status, patients who were treated in an experimental arm that included adjuvant immunotherapy had similar EFS. CONCLUSIONS:Our study reported a strong EFS improvement in patients who achieved either pCR or MPR after neoadjuvant chemoimmunotherapy. The use of adjuvant immunotherapy after tumor resection was not associated with improved EFS.