Systematic Review and Meta-Analysis of Immune Checkpoint Inhibitors As Single Agent or in Combination With Chemotherapy in Early-Stage Non-small Cell Lung Cancer: Impact of Clinicopathological Factors and Indirect Comparison Between Treatment Strategies

Authors

Antonio Nuccio
Giuseppe Viscardi
Fabio Salomone
Alberto Servetto
Francesco Maria Venanzi
Silvia Teresa Riva
Sara Oresti
Francesca Rita Ogliari
Mariagrazia Viganò
Alessandra Bulotta
Robert Cameron
Alessandra Esposito
Jacobi Hines
Roberto Bianco
Michele Reni
Tina Cascone
Marina Chiara Garassino
Valter Torri
Giulia Veronesi
Michela Cinquini
Roberto Ferrara

Language

English

Publication Date

12-1-2023

Journal

European Journal of Cancer

DOI

10.1016/j.ejca.2023.113404

PMID

37948842

PMCID

PMC12697757

PubMedCentral® Posted Date

12-12-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Background: In non-small cell lung cancer (NSCLC), the immune checkpoint inhibitors (ICI) revolution is rapidly moving from metastatic to early-stage, however, the impact of clinicopathological variables and optimal treatment sequencing remain unclear.

Methods: Randomized controlled trials (RCTs) in patients with early-stage NSCLC treated with ICI as single agent or in combination with platinum-based chemotherapy (PCT) were included. Primary outcomes were pathological complete response (pCR), event free survival (EFS) (neoadjuvant/perioperative), and disease-free survival (DFS) (adjuvant). Secondary outcomes were major pathological response (MPR), overall survival (OS), toxicity, surgical outcomes (neoadjuvant/perioperative); OS and toxicity (adjuvant). An additional secondary endpoint was to compare EFS and OS between neoadjuvant and perioperative strategies.

Results: 8 RCTs (2 neoadjuvant, 4 perioperative, 2 adjuvant) (4661 participants) were included. Neoadjuvant/perioperative ICI+PCT significantly improved pCR, EFS, OS, MPR and R0 resection compared to PCT. Adjuvant ICI significantly improved DFS compared to placebo. There was a significant subgroup interaction by PD-L1 status (χ2 = 10.72, P = 0.005), pCR (χ2 = 17.80, P < 0.0001), and stage (χ2 = 4.46, P = 0.003) for EFS. No difference according to PD-L1 status was found for pCR, with 14% of patients having PD-L1 negative tumors still experiencing a pCR. No interaction by PD-L1 status was found for DFS upon adjuvant ICI. Indirect comparison showed no difference in EFS and OS between neoadjuvant and perioperative ICI+PCT.

Conclusions: PD-L1 status, pCR and stage impact on survival upon neoadjuvant/perioperative ICI. The restriction of neoadjuvant/perioperative ICI to PD-L1 + patients could preclude pCR and long-term benefit in the PD-L1- subgroup. Neoadjuvant and perioperative could be equivalent strategies.

Keywords

Humans, Immune Checkpoint Inhibitors, B7-H1 Antigen, Carcinoma, Non-Small-Cell Lung, Neoadjuvant Therapy, Small Cell Lung Carcinoma, Adjuvants, Immunologic, Lung Neoplasms, Neoadjuvant, Adjuvant, NSCLC, Immune checkpoint inhibitors, Meta-analysis, Early-stage, pCR

Published Open-Access

yes

Recommended Citation

Nuccio, Antonio; Viscardi, Giuseppe; Salomone, Fabio; et al., "Systematic Review and Meta-Analysis of Immune Checkpoint Inhibitors As Single Agent or in Combination With Chemotherapy in Early-Stage Non-small Cell Lung Cancer: Impact of Clinicopathological Factors and Indirect Comparison Between Treatment Strategies" (2023). Faculty, Staff and Student Publications. 5439.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5439