Stereotactic Ablative Body Radiotherapy for Oligoprogressive Estrogen Receptor–Positive Breast Cancer (TROG 20.03 AVATAR): A Phase II Prospective Multicenter Trial

PURPOSE AVATAR (trial registration: ACTRN 12620001212943) is a multicenter phase II single-arm trial to evaluate whether stereotactic ablative body radiotherapy (SABR) for oligoprogressive estrogen receptor (ER)–positive human epidermal growth factor receptor 2 (HER2)–negative breast cancer can delay a change from combination cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and an aromatase inhibitor (AI) to next-line systemic therapy. METHODS Patients received SABR to all sites of oligoprogressive disease while continuing CDK 4/6i and AI therapy. SABR was permitted for further oligoprogression without altering systemic therapy. The primary end point was event-free survival defined as the time from SABR to either (1) a change in systemic therapy, (2) any progression within 6 months, or (3) the appearance of >3 new progressing lesions. A key secondary end point was modified progression-free survival (mPFS), defined as oligoprogression not amenable to further SABR, or death due to any cause. RESULTS Thirty-two eligible patients were recruited between August 2020 and November 2022, with a median follow-up of 24 months. The primary end point was met, with 47% (95% CI, 29 to 63) of patients remaining event-free for ≥6 months. The median mPFS was 9.9 months (95% CI, 4.1 to not reached), with an estimated 44% (95% CI, 26 to 60) and 36% (95% CI, 20 to 53) of patients maintaining systemic therapy unchanged for 12 and 24 months, respectively. Median PFS was 5.2 months (95% CI, 3.1 to 6.8), with 11 (34%) and two (6%) of patients receiving second and third courses of SABR, respectively. No grade 3 or higher toxicities were reported. CONCLUSION In patients with oligoprogressive ER-positive, HER2-negative breast cancer, these findings suggest that SABR is a viable strategy to maintain treatment with CDK 4/6i in lieu of a change in systemic therapy.