ImmunoChemoradiation for Non-Small Cell Lung Cancer: A Meta-Analysis of Factors Influencing Survival Benefit in Combination Trials

Huei-Tyng Huang; Douglas H Brand; John D Fenwick; Maria A Hawkins

doi:10.1016/j.ijrobp.2024.03.029

ImmunoChemoradiation for Non-Small Cell Lung Cancer: A Meta-Analysis of Factors Influencing Survival Benefit in Combination Trials

Int J Radiat Oncol Biol Phys. 2024 Apr 2:S0360-3016(24)00449-8. doi: 10.1016/j.ijrobp.2024.03.029. Online ahead of print.

Authors

Huei-Tyng Huang¹, Douglas H Brand², John D Fenwick³, Maria A Hawkins⁴

Affiliations

¹ Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom.
² Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom; University College London Hospital NHS Foundation Trust, London, United Kingdom.
³ Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom. Electronic address: john.fenwick@ucl.ac.uk.
⁴ Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom; University College London Hospital NHS Foundation Trust, London, United Kingdom. Electronic address: m.hawkins@ucl.ac.uk.

PMID: 38570169
DOI: 10.1016/j.ijrobp.2024.03.029

Abstract

Purpose: Adding immune checkpoint blockade (ICB) to concurrent chemoradiotherapy (cCRT) has improved overall survival (OS) for inoperable locally advanced non-small cell lung cancer. Trials of cCRT-ICB are heterogeneous for factors such as tumor stage and histology, programmed cell death ligand-1 (PDL-1) status, and cCRT-ICB schedules. We therefore aimed to determine the ICB contribution to survival across studies and identify factors associated with survival gain.

Methods and materials: Data were collated from cCRT-ICB clinical studies published 2018 to 2022 that treated 2196 patients with non-small cell lung cancer (99% stage 3). Associations between 2-year OS and ICB, CRT, patient and tumor factors were investigated using metaregression. A published model of survival after radiation therapy (RT) or CRT was extended to include ICB effects. The model was fitted simultaneously to the cCRT-ICB data and data previously compiled for RT/CRT treatments alone. The net ICB contribution (OS gain) and its associations with factors were described by fitted values of ICB terms added to the model. Statistical significance was determined by likelihood-ratio testing.

Results: The gain in 2-year OS from ICB was 9.9% overall (95% CI, 7.6%, 12.2%; P = .018). Both OS gain and 2-year OS itself rose with increasing planned ICB duration (P = .008, .002, respectively) and with tumor PDL-1 ≥ 1% (P = .034, .023). Fitted OS gains were also greater for patients with stage 3B/C disease (P = .021). OS gain was not associated with tumor histology, patient performance status, radiation therapy dose, ICB drug type (anti-PDL-1 vs anti-programmed cell death-1), or whether ICB began concurrently with or after cCRT.

Conclusions: Fitted gains in 2-year OS due to ICB were higher in cohorts with greater fractions of stage 3B/C patients and patients with tumor PDL-1 ≥ 1%. OS gain was also significantly higher in a single cohort with a planned ICB duration of 2 years rather than 1, but was not associated with whether ICB treatment began during versus after CRT.