Combined immune checkpoint inhibitors and ablative radiotherapy in metastatic cancers: a meta-analysis of prospective clinical trials.

Objective: To pool data from prospective clinical trials investigating combined stereotactic ablative radiotherapy (SABR) with immune checkpoint inhibitors (ICI) in patients with metastatic cancers.

Methods and analysis: PubMed, Scopus and EMBASE were queried for full-length articles of prospective clinical trials involving patients with metastatic solid tumours. Random-effects meta-analysis was performed with the Knapp-Hartung method. Multilevel regression analyses with primary cancers used as random effects and pairwise comparisons with two-tailed test adjusted with Benjamini-Hochberg method were performed. Regression coefficients (β) were calculated to assess the correlation between dose and outcomes.

Results: We identified 30 trials and 35 individual treatment arms with a total of 951 patients with at least one outcome metric reported. Large heterogeneity was identified for all outcomes measured (I² range: 75%-86%). The pooled rate of grade 3+ treatment-related adverse events was 18% (95% CI 11% to 24%). The progression-free survival (PFS) and overall survival (OS) at 6 months were 27% (95% CI 19% to 36%) and 67% (95% CI 59% to 76%), respectively. On multilevel regression, we identified improvement in 6-month PFS (β=0.6, p=0.003) and OS (β=1.6, p=0.04) with increasing BED10Gy doses. Combined-target ICI correlated with better 6-month OS when compared with αPD-1/PD-L1 alone.

Conclusion: We report a safety profile of combined ICI with SABR in patients with metastatic cancer that is comparable to that of ICI alone. We identified higher doses of radiotherapy and dual-target ICI to be associated with better OS at 6 months. Large heterogeneity and the lack of a control group limit the interpretation of our findings.