Immunotherapy with or after chemoradiotherapy (CRT) vs CRT alone in limited-stage small cell lung cancer (SCLC): Meta-analysis of randomized controlled trials.

Abstract

e20140 Background: Limited-stage SCLC is treated with curative-intent concurrent chemoradiation (CRT). However, relapse is still common. We evaluated the efficacy and safety of adding immune checkpoint inhibitors (ICI) versus CRT control. Methods: PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials enrolling adults with limited-stage SCLC treated with definitive concurrent CRT and randomized to ICI versus no-ICI control. Trials evaluated ICI given either concurrently with or as adjuvant therapy after CRT with atezolizumab, or as post-CRT consolidation/maintenance therapy with durvalumab in one trial and nivolumab plus ipilimumab in another, each compared to no-ICI control. One eligible RCT was available as an ASCO 2025 abstract (Grønberg et al.; NCT03540420). Primary endpoint was overall survival (OS); secondary endpoint was progression-free survival (PFS). Safety outcomes included grade ≥3 adverse events (AEs), grade ≥3 pneumonitis, and fatal events as reported (treatment-related death or AEs with outcome of death). Time-to-event outcomes were pooled as hazard ratios (HRs), and binary outcomes as risk ratios (RRs), using a DerSimonian and Laird for random-effects, heterogeneity was assessed with I². Safety event counts are summarized in Table 1. Results: Four RCTs (N = 1,371) were included. Overall, immunotherapy did not significantly improve OS HR 0.93 (95% CI 0.77-1.14; I² = 28.7%) or PFS HR 0.89 (95% CI 0.78-1.03; I² = 0%). There was a statistically higher incidence of grade ≥3 pneumonitis RR 1.98 (95% CI 1.02-3.84; I² = 0%) and fatal events RR 3.29 (95% CI 1.47-7.36; I² = 15.5%). Grade ≥3 AEs were non-significantly higher in the ICI group RR 1.29 (95% CI 0.86-1.95; I² = 87.4%). Conclusions: In limited-stage SCLC, adding immunotherapy did not improve OS or PFS. High-grade (grade ≥3) adverse events were non-significantly increased, whereas pneumonitis and fatal events were significantly increased. Safety outcomes across included RCTs (events/total; ICI vs control). Trial Grade ≥3 AEs Grade ≥3 Pneumonitis Fatal Events Peters et al, 2022 48/78 vs 19/75 7/78 vs 1/75 4/78 vs 1/75 Cheng et al, 2024 64/262 vs 64/265 3/262 vs 2/265 7/262 vs 5/265 Grønberg et al, 2025 Not Reported 2/85 vs 2/85 3/85 vs 0/85 Higgins et al, 2026 253/264 vs 242/257 16/264 vs 8/257 24/264 vs 4/257 Total 365/604 vs 325/597 28/689 vs 13/682 38/689 vs 10/682