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Meta-Analysis
. 2025 Mar 11:218:115266.
doi: 10.1016/j.ejca.2025.115266. Epub 2025 Jan 30.

Efficacy and safety of immune checkpoint inhibition combined with concurrent chemoradiotherapy in patients with stage III unresectable non-small cell lung cancer: A systematic review and meta-analysis

Fabian Acker  1 , Martin Reck  2 , Daniel Martin  3 , Stefan Rieken  4 , Sophie Heinzen  5 , Maximilian Rost  5 , Lukas Aguinarte  5 , Hanna Schulte  5 , Hubert Serve  5 , Thomas Oellerich  5 , Martin Sebastian  5 , Friederike C Althoff  5
Affiliations
Free article
Meta-Analysis

Efficacy and safety of immune checkpoint inhibition combined with concurrent chemoradiotherapy in patients with stage III unresectable non-small cell lung cancer: A systematic review and meta-analysis

Fabian Acker et al. Eur J Cancer. .
Free article

Abstract

Background: In patients with unresectable, stage III non-small cell lung cancer (NSCLC), durvalumab maintenance after concurrent chemoradiotherapy (cCRT) was shown to improve survival over placebo. As subgroup analyses indicated better outcomes with earlier start of durvalumab, several trials evaluated concomitant checkpoint inhibition (CPI) with cCRT. However, this may introduce an increased risk of treatment-related pulmonary toxicity.

Methods: We conducted a systematic review and meta-analysis of clinical trials of combined cCRT plus CPI followed by CPI maintenance in patients with stage III NSCLC. Endpoints included incidence of pneumonitis by any cause, objective response rate (ORR), progression-free (PFS), and overall survival (OS).

Results: A total of 7 trials comprising 653 patients were included. In trials of single-agent CPI with cCRT, pneumonitis occurred in 33 % of patients (95 % confidence interval [CI], 28-39) with 7 % (5-9) having CTCAE grade 3-5. In one trial, double CPI (PD-1 and CTLA4) plus cCRT was associated with excessive pneumonitis-related mortality of 16 % (4-40). Across all trials, ORR was 69 % (63-76). Median PFS and OS were 16.3 (95 % CI, 14.0-20.5) and 39.5 months (35.3-45.9), respectively. Three-year PFS and OS were 36.8 % (95 % CI, 32.7-41.4) and 53.1 % (49.1-57.4). Sensitivity analysis showed that induction chemoimmunotherapy prior cCRT plus CPI was associated with improved PFS of 48.0 % at 3 years (95 % CI, 40.7-56.7) in one trial.

Discussion: Addition of single-agent CPI to cCRT is manageable in selected patients with stage III NSCLC. Efficacy outcomes appear to be in line with previous data of cCRT followed by CPI maintenance.

Keywords: Checkpoint inhibitor; Chemoradiotherapy; Locally advanced; Meta-analysis; NSCLC; Stage III; Systematic review.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F.A. reports having received support for attending meetings from AstraZeneca, Amgen, and Daiichi-Sankyo, speaker’s honoraria from AstraZeneca, and Amgen, and consultant fees from IQVIA and Novartis. M. Reck reports having received honoraria for lectures and consultation fees from AstraZeneca, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, GSK, Lilly, Merck, Merck Sharp & Dohme, Mirati, Novartis, Pfizer, Roche, and Regeneron. D.M. reports having received speaker’s honoraria from AstraZeneca. S.R. reports having received honoraria for lectures and consultation fees from AstraZeneca, Novocure, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. S.H. reports having no conflicts of interest. M. Rost reports having no conflicts of interest. L.A. reports having no conflicts of interest. H.Sc. reports having no conflicts of interest. H.Se. reports having no conflicts of interest. T.O. reports having received research funding from Gilead and Merck KGaA, consultation fees from Beigene, Roche, Janssen, Merck KGaA, Gilead, Kronos Bio, and Abbvie. M.S. reports having received a research grant from AstraZeneca, support for attending meetings from Pfizer, Takeda, and Merck, speaker’s honoraria from Roche, Boehringer Ingelheim, AstraZeneca, Sanofi, GSK, and Merck, and consultant fees from Novartis, BMS, Boehringer Ingelheim, Pfizer, AstraZeneca, Takeda, Pierre Fabre, Gilead, Daiichi-Sankyo, and Sanofi. F.C.A. reports having received a research grant from Novartis, research funding from Gilead, speaker’s honoraria from Roche and Amgen, support for attending meetings and/or travel from Amgen, and consultant fees from IQVIA, outside of the submitted work.

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