Immuno-chemoradiation for non-small cell lung cancer: A meta-analysis of factors influencing survival benefit in combination trials

Purpose Adding immune checkpoint blockade (ICB) to concurrent chemoradiotherapy (cCRT) has improved overall survival (OS) for inoperable locally advanced non-small cell lung cancer (LA-NSCLC). Trials of cCRT-ICB are heterogeneous for factors such as tumor stage and histology, PDL1 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 2018-2022 which treated 2196 NSCLC patients (99% stage III). Associations between 2-year OS and ICB, CRT, patient and tumor factors were investigated using meta-regression. A published model of survival following 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=0.018). Both OS gain and 2-year OS itself rose with increasing planned ICB duration (p=0.008, 0.002 respectively) and with tumor PDL1 ≥1% (p=0.034, 0.023). Fitted OS gains were also greater for patients with stage IIIB/C disease (p=0.021). OS gain was not associated with tumor histology, patient performance status, RT dose, ICB drug type (anti-PDL1 vs anti-PD1) or whether ICB began concurrently with or after cCRT. Conclusion Fitted gains in 2-year OS due to ICB were higher in cohorts with greater fractions of stage IIIB/C patients and patients with tumor PDL1 ≥1%. OS gain was also significantly higher in a single cohort with a planned ICB duration of two years rather than one, but was not associated with whether ICB treatment began during vs after CRT.