Consolidation PD-(L)1 inhibitor after definitive chemoradiotherapy for unresectable stage III NSCLC: Systematic review and meta-analysis of randomized controlled trials.

Abstract

e20054 Background: Consolidation immune checkpoint inhibition after definitive chemoradiotherapy (CRT) improves outcomes in unresectable stage III non-small cell lung cancer (NSCLC). With newer randomized evidence, we evaluated the efficacy and safety of consolidation PD-(L)1 inhibitors versus placebo after definitive CRT. Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials enrolling adults with unresectable stage III NSCLC without progression after definitive CRT and randomized to consolidation PD-(L)1 inhibitor versus placebo. PFS and OS were pooled as hazard ratios (HRs) and discontinuation due to adverse events (AEs) as risk ratios (RRs) using DerSimonian-Laird random-effects; heterogeneity was assessed with I². Treatment-related deaths were summarized descriptively. Results: Three RCTs (N = 1,501) were included (PACIFIC, GEMSTONE-301, PACIFIC-5). Consolidation PD-(L)1 inhibition improved PFS (pooled HR 0.63, 95% CI 0.53-0.77; I² = 40.5%). OS favored PD-(L)1 inhibition (pooled HR 0.69, 95% CI 0.52-0.93) but was interim/immature in two trials with substantial heterogeneity (I² = 63%). Discontinuation due to AEs was higher with PD-(L)1 inhibition (pooled RR 1.72, 95% CI 1.23-2.40; I² = 0%). Treatment-related deaths were rare and reported in two trials (8/526 vs 0/260; GEMSTONE-301: 4/255 vs 0/126; PACIFIC-5: 4/271 vs 0/134). Conclusions: Consolidation PD-(L)1 inhibition after definitive CRT significantly improves PFS in unresectable stage III NSCLC, with an OS signal that requires longer follow-up. Discontinuation due to AEs is increased. Longer follow-up is needed to clarify long-term survival outcomes and infrequent safety events. Sugemalimab is approved for NSCLC indications in China and the UK but is not FDA-approved in the US. Trial-level efficacy (HRs) and AE-discontinuation (counts and RRs). Footnote: Time-to-event outcomes pooled as HRs. OS was interim/immature in GEMSTONE-301 and PACIFIC-5. AE-discontinuation uses reported safety-set denominators (PACIFIC-5 efficacy mITT differs from safety set). Treatment-related deaths were not pooled. RCT Agent N (Tx/Placebo) PFS HR (95% CI) OS HR (95% CI) Discontinuation due to AEs (Tx vs placebo) RR (95% CI) PACIFIC Durvalumab 476/237 0.55 (0.45-0.68) 0.72 (0.59-0.89) 73/475 vs 23/234 1.56 (1.01-2.43) GEMSTONE-301 Sugemalimab 255/126 0.64 (0.48-0.85) 0.44 (0.27-0.73) 29/255 vs 6/126 2.39 (1.02-5.60) PACIFIC-5 Durvalumab 252/129 (mITT); 271/134 (safety) 0.75 (0.58-0.99) 0.87 (0.66-1.17) 39/271 vs 11/134 1.75 (0.93-3.31) Pooled (DL random-effects) - - 0.63 (0.53-0.77) 0.69 (0.52-0.93) - 1.72 (1.23–2.40); I²=0%