3038 - Immune Checkpoint Inhibitors Administered Prior to Chemoradiotherapy Increase Radiation-Induced Pneumonitis Risk in Stage III Unresectable NSCLC

Purpose/Objective(s): The PACIFIC trial supports immune checkpoint inhibitor (ICI) consolidation after concurrent chemoradiotherapy (cCRT), but the toxicity risks of earlier ICI timing, as in AFT-16, remain unclear. ICI can be given following, concurrently with, or prior to cCRT, with concerns about increased radiation-induced pneumonitis (RP). This study aims to determine if earlier ICI administration raises RP risk post-cCRT, hypothesizing a correlation between earlier ICI timing and higher RP incidence.

Materials/Methods: RP was graded according to the Common Terminology Criteria for Adverse Events, version 5.0. Patients were divided into three groups: ICI following cCRT, ICI concurrent with cCRT, and ICI prior to cCRT. A search of PubMed, Embase, Web of Science, and ClinicalTrials.gov identified studies on stage III unresectable non-small cell lung cancer (NSCLC) patients receiving cCRT and ICI. Meta-analysis inclusion criteria were: (1) Prospective/retrospective studies on stage III unresectable NSCLC; (2) cCRT and ICI treatment; (3) Reported RP incidence. Sequential chemoradiotherapy studies were excluded. Additionally, validation data from 170 stage III NSCLC patients from a single-center cohort study were analyzed for = 2 grade RP using Kaplan-Meier curves and Cox regression.

Results: The results of the study are shown in Table. The group that received ICI prior to cCRT exhibited significantly elevated rates. In the clinical retrospective study, after adjusting for factors (age, tumor staging, performance status, and radiation dose, etc.), early administration of ICI still resulted in an increased incidence of RP. Furthermore, a shorter interval between ICI and radiotherapy was associated with a higher incidence of RP.

Conclusion: Earlier ICI administration increases the risk of = grade 2 RP following cCRT in stage III unresectable NSCLC patients. This study suggests balancing survival benefit and pulmonary toxicity, avoiding early ICI treatment. These findings will guide future randomized controlled trials design. However, limitations include the single-arm meta-analysis, potential bias in retrospective data, and small sample size, which should be considered when interpreting the results.