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 (I 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.