3626 - Impact of Immunotherapy Timing on Survival after Definitive Chemoradiotherapy in Unresectable Stage III NSCLC: A Systematic Review and Meta-Analysis
Presenter(s)
Simran1,2, K. Shin3, S. Panda4, L. Martinka1,5, K. Olabode1,5, J. Gray6, A. N. Saltos6, S. Puri6, B. Creelan6, A. Chiappori6, C. Lu6, M. Shafique6, S. A. Rosenberg1, S. K. Jabbour7, T. J. Dilling1, T. Tanvetyanon6, and J. Kim8,9; 1Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 2Department of Radiation Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India, 3Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4All India Institute of Medical Sciences(AIIMS), Raipur, Raipur, India, 5Morsani College of Medicine, University of South Florida, Tampa, FL, 6Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 7Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, NJ, 8Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, 9Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Purpose/Objective(s):
Consolidation immune checkpoint inhibition following definitive concurrent chemoradiotherapy (CRT) is the standard of care for unresectable stage III non–small cell lung cancer (NSCLC), based on the PACIFIC trial, which mandated initiation of immunotherapy within 42 days of CRT completion. In real-world practice, however, treatment delays are common, and the impact of delayed immunotherapy initiation on survival outcomes remains unclear. We performed a systematic review and meta-analysis to evaluate whether early versus delayed initiation of consolidation immunotherapy impacts survival outcomes in unresectable stage III NSCLC.Materials/Methods:
PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL were searched from inception through January 2026. Eligible studies included randomized or observational cohorts reporting survival stratified by timing of PD-1/PD-L1 inhibitor initiation after definitive CRT (radiation dose =60 Gy or equivalent). The primary endpoint was overall survival (OS). Hazard ratios (HRs) were pooled using an inverse-variance random-effects model.Results:
Three retrospective cohort studies—Qin 2025 (n=185), Stevens 2022 (n=145), and Tanvetyanon 2025 (n=854)—met inclusion criteria, comprising 1,184 patients; 928 (78.4%) received consolidation immunotherapy. Pooled Median follow up time was 23.8 months (range 18.9-28.6). Stevens and Tanvetyanon evaluated sequential durvalumab (PD-L1 inhibitor) exclusively, whereas Qin included both PD-1 and PD-L1 inhibitors and concurrent and sequential strategies; only the sequential subgroup contributed to the pooled timing analysis. The weighted median age was 69 years (range 61–71), and 91% had ECOG 0–1 performance status. The pooled median time to immunotherapy initiation was 49 days (range 39–59). Random-effects meta-analysis from Stevens 2022 and Tanvetyanon 2025 demonstrated a statistically significant overall survival benefit with earlier initiation (HR 0.77, 95% CI 0.61–0.98; p = 0.034), corresponding to a 23% relative reduction in mortality risk. Qin additionally demonstrated a time-dependent increase in mortality risk per day of delay (adjusted HR 1.002 per day; 95% CI 1.001–1.003; p = 0.002), supporting a graded survival disadvantage with prolonged interval to immunotherapy.Conclusion:
In this meta-analysis of real-world cohorts, earlier initiation of consolidation PD-1/PD-L1 inhibition after definitive CRT was associated with significantly improved overall survival in unresectable stage III NSCLC. Analyses modeling time to initiation as a continuous variable demonstrated a graded increase in mortality risk with each additional day of delay. These findings support the timely initiation of consolidation immunotherapy after definitive CRT and underscore the importance of minimizing avoidable treatment delays while awaiting prospective validation.