Objective: To assess if stereotactic ablative body radiotherapy (SABR) for oligoprogressive luminal (ER positive, Her-2 negative) advanced breast cancer could delay a change in combination CDK 4/6 inhibitor and an aromatase inhibitor therapy (CDK 4/6 + AI) by = 6 months in > 25% of patients. Herein we report the primary outcome.
Methods: AVATAR enrolled eligible patients with advanced luminal breast cancer who received first- or second-line systemic treatment in the metastatic setting with a CDK 4/6 + AI for = 6 months. Patients required an ECOG performance status of 0-2 and 1-5 extracranial oligoprogressing lesions amenable to SABR. Patients who had chemotherapy for metastatic disease, leptomeningeal disease, or prior radiotherapy to an oligoprogressing lesion planned for SABR were excluded. At subsequent progression, further SABR was permitted to delay a change in systemic therapy. The primary endpoint was event free survival (EFS) defined as a time to change in systemic therapy after SABR, any progression within 6 months or in > 3 lesions. Secondary endpoints were progression free survival (PFS), overall survival (OS), treatment related toxicity and modified progression free survival (mPFS) defined as progression not amenable to further SABR at any time.
Results: 32 patients were recruited with a median follow-up of 15.8 months. The most common sites of oligoprogression were bone 44 (71%), and nodal 11 (18%). The most common SABR doses were 20 Gy /1 fraction and 24 Gy/2 fractions. The null hypothesis was rejected, with 47% (95% CI: 29-65) of patients remaining event free for = 6 months. The median mPFS was 10.4 months (95% CI: 4.1-not reached) with 46% (95% CI: 27-63) remaining unchanged on systemic therapy for 12 months. Median PFS was 5.2 months (95% CI: 3.1-6.8), with 10/30 (33%) progressions suitable for a second course of SABR for oligoprogression to further delay systemic therapy change.
Conclusion: This is the first prospective trial investigating SABR as a strategy to maintain CDK 4/6 + AI in patients with oligoprogessive luminal breast cancer. This approach was well tolerated, with a higher than anticipated median time to change in systemic therapy of 10.4 months, and 46% of patients maintained on a CDK 4/6 + AI for 12 months. These findings suggest that patients with oligoprogressive luminal breast cancer should be considered for SABR in lieu of a change in systemic therapy.