Efficacy and safety of sequential versus concurrent administration of immune checkpoint inhibitors with radiotherapy in solid tumors: a systematic review and network meta-analysis.

backgroundImmune checkpoint inhibitors (ICIs) combined with radiotherapy (RT) enhance antitumor efficacy; however, the optimal sequencing of these treatments remains undefined. We conducted a network meta-analysis (NMA) of randomized controlled trials to compare the efficacy and safety of ICIs administered after completion of RT versus those administered concurrently with RT.

methodsA search of PubMed, Embase, Cochrane Library (CENTRAL), and ClinicalTrials.gov identified studies published through February 5, 2025. The primary outcome was overall survival (OS); the secondary outcome was progression-free survival (PFS); safety was assessed by the incidence of grade ≥ 3 adverse events (AEs).

resultsThis NMA included 24 randomized controlled trials involving 9,480 participants. The sequential ICI arm significantly improved OS (hazard ratio (HR): 0.81 [95% confidence interval (CI) 0.72 to 0.92]) and PFS (HR: 0.73 [95% CI 0.64 to 0.84]) versus the control arm, whereas the concurrent ICI arm showed no significant benefit. Compared with the concurrent ICI arm, the sequential ICI arm showed significantly superior PFS (HR: 0.81 [95% CI 0.67 to 0.97]). Additionally, the sequential ICI arm showed no statistically significant difference in grade ≥ 3 AE rates compared with the concurrent ICI arm (odds ratio (OR): 1.02 [95% CI 0.56 to 1.85]).

conclusionsCompared with concurrent administration of ICI with RT, sequential administration of ICI after RT improves survival outcomes without increasing toxicity. Further studies are needed to define the optimal timing of RT and ICIs to maximize efficacy while minimizing AEs.