The survival impact of combining radiotherapy and immune checkpoint inhibitors in patients with solid tumors: A systematic review and living meta-analysis of randomized controlled trials

Abstract

Background: Preclinical studies indicate synergistic effects of radiotherapy and immune checkpoint inhibitors (ICIs), yet randomized trials have yielded inconsistent results. We conducted a living systematic review and meta-analysis to evaluate the survival impact of combining radiotherapy with ICIs versus radiotherapy or ICIs alone in solid tumors.

Methods: PubMed and EMBASE were searched for randomized trials (January 2010-January 2026), evaluating two strategies: (1) addition of ICIs to a radiotherapy backbone (immunotherapy trials), and (2) addition of radiotherapy to an ICI backbone (radiotherapy trials). Risk of bias was assessed with RoB-2. Hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were pooled using random-effects models. Meta-regression explored subgroup effects.

Results: Of 4447 unique records, 41 trials (15,049 patients) were included: 35 ICIs versus no ICIs and 6 radiotherapy versus no radiotherapy trials. Methodological quality was high. Across ICI trials, the pooled HR for OS was 0.88 (95%CI 0.75-1.02; n = 28), reaching statistical significance after exclusion of glioblastoma trials (pooled HR 0.83, 95%CI 0.70-0.99; n = 23). For PFS and EFS, pooled HRs were 0.80 (95%CI 0.68-0.93; n = 27) and 0.73 (95%CI 0.55-0.99; n = 7), respectively. Adjuvant ICIs conferred greater benefit than concurrent/induction for OS (pooled HR 0.81 versus 0.98; interaction p = 0.045) and PFS (pooled HR 0.69 versus 0.94; interaction p = 0.013).

Conclusions: This meta-analysis provides a field-wide overview of randomized trials on combining radiotherapy and ICIs. Addition of ICIs to a radiotherapy backbone improves PFS/EFS and yields an OS benefit after exclusion of glioblastoma trials, highlighting tumor-specific heterogeneity. Sequencing appears critical, with greatest benefit observed for adjuvant ICIs. The living meta-analysis is available at https://www.immunorad.org/clinical-evidence.

Keywords: Immune checkpoint inhibitors; Meta-analysis; Radiotherapy; Solid tumors; Survival.