Single-fraction or multi-fraction stereotactic ablative body radiotherapy followed by atezolizumab in advanced triple-negative breast cancer: a randomized phase II trial.

Pre-clinical evidence suggests that stereotactic ablative body radiotherapy (SABR) can enhance systemic anti-tumor responses when combined with immune checkpoint inhibition, although optimal fractionation remains uncertain. Here we conducted a phase II multi-center randomized trial (AZTEC trial; ClinicalTrials.gov identifier NCT03464942) to investigate the efficacy and safety of single-fraction (SF: 20 Gy; n = 27) or multi-fraction (MF: 24 Gy in three fractions; n = 27) SABR followed by anti-PD-L1 atezolizumab in 54 women with advanced triple-negative breast cancer (TNBC) as first or second-line treatment. The primary endpoint was progression free survival (PFS). Secondary endpoints included best overall response rate, clinical benefit rate, overall survival and safety. We observed that both treatment arms had similar efficacy: median PFS was 2.5 months (90% CI: 1.7-4.5) for SF and 3.1 months (90% CI: 1.8-3.9) for MF. The null hypothesis (PFS of 2 months) was not rejected in either arm. Clinical benefit (RECIST complete response/partial response or stable disease for ≥24 weeks) was achieved in 5 (20%) SF and 6 (25%) MF patients, all with oligometastatic disease, independent of PD-L1 expression. Adverse events were similar between arms. Prespecified exploratory analysis of peripheral blood found higher CD8 TPEX cells before and during treatment correlated with improved response duration. Combining SABR with atezolizumab is safe, however further testing is required to determine efficacy for advanced TNBC patients with oligometastatic disease.