Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials
Daniele Marinelli, Filippo Tommaso Gallina, Sergio Pannunzio, Mattia Alberto Di Civita, Andrea Torchia, Raffaele Giusti, Alain Gelibter, Michela Roberto, Monica Verrico, Enrico Melis, Riccardo Tajè, Fabiana Letizia Cecere, Lorenza Landi, Paola Nisticò, Nicla Porciello, Mario Occhipinti, Marta Brambilla, Patrick M. Forde, Stephen V. Liu, Andrea Botticelli, Silvia Novello, Gennaro Ciliberto, Enrico Cortesi, Francesco Facciolo, Federico Cappuzzo, Daniele Santini
Abstract
The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade > = 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint. • Perioperative ICIs plus with neoadjuvant chemotherapy improves surgical outcomes. • Perioperative ICIs plus with neoadjuvant chemotherapy improves pCR, EFS and OS. • PD-L1 negative NSCLC benefits from chemoimmunotherapy combinations. • Higher rates of grade > = 3 adverse events were associated with experimental treatment. • Confirmatory evidence is warranted in stage IIIB tumours.