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. 2025 Apr;27(4):1516-1528.
doi: 10.1007/s12094-024-03712-0. Epub 2024 Sep 12.

Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials

Yunchang Meng #  1 , Hedong Han #  2 , Suhua Zhu #  2 , Chuling Li  2 , Huijuan Li  2 , Zhaofeng Wang  2 , Ranpu Wu  3 , Yimin Wang  1 , Qingfeng Zhang  2 , Yanzhuo Gong  4 , Yong Song  2 , Tangfeng Lv  5   6 , Hongbing Liu  7   8
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Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials

Yunchang Meng et al. Clin Transl Oncol. 2025 Apr.

Abstract

Purpose: This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC).

Methods: Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR).

Results: Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42).

Conclusion: Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.

Keywords: Immune checkpoint inhibitors (ICIs); Immunotherapy; Network meta-analysis; Non-small cell lung cancer (NSCLC); Perioperative; Resectable.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article. Ethics approval and consent to participate: The study did not involve specific human participants and ethical review board review and approval was not applicable. Written informed consent was not required for this study in accordance with national legal and institutional requirements. Consent for publication: This study does not contain any individual person’s data in any form (including individual details, images or videos).

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