Does major pathological response after neoadjuvant Immunotherapy in resectable nonsmall-cell lung cancers predict prognosis? A systematic review and meta-analysis

Objective: Overall survival is the gold-standard outcome measure for phase 3 trials, but the need for a long follow-up period can delay the translation of potentially effective treatment to clinical practice. The validity of major pathological response (MPR) as a surrogate of survival for non small cell lung cancer (NSCLC) after neoadjuvant immunotherapy remains unclear. Methods: Eligibility was resectable stage I-III NSCLC and delivery of PD-1/PD-L1/CTLA-4 inhibitors prior to resection; other forms/modalities of neoadjuvant and/or adjuvant therapies were allowed. Statistics utilized the Mantel-Haenszel fixed-effect or random-effect model depending on the heterogeneity (I-2). Results: Fifty-three trials (seven randomized, 29 prospective nonrandomized, 17 retrospective) were identified. The pooled rate of MPR was 53.8%. Compared to neoadjuvant chemotherapy, neoadjuvant chemo-immunotherapy achieved higher MPR (OR 6.19, 4.39-8.74, P<0.00001). MPR was associated with improved disease-free survival/progression-free survival/event-free survival (HR 0.28, 0.10-0.79, P=0.02) and overall survival (HR 0.80, 0.72-0.88, P<0.0001). Patients with stage III (vs I/II) and PD-L1 >= 1% (vs <1%) more likely achieved MPR (OR 1.66,1.02-2.70, P=0.04; OR 2.21,1.28-3.82, P=0.004). Conclusions: The findings of this meta-analysis suggest that neoadjuvant chemo-immunotherapy achieved higher MPR in NSCLC patients, and increased MPR might be associated with survival benefits treated with neoadjuvant immunotherapy. It appears that the MPR may serve as a surrogate endpoint of survival to evaluate neoadjuvant immunotherapy.