A phase 1 dose-escalation trial of radiotherapy with concurrent PARP inhibition in patients with triple-negative breast cancer with residual disease after neoadjuvant chemotherapy, recently published in JAMA Oncology, show that the combination of olaparib and radiotherapy is a feasible and well tolerated approach in these patients.
Triple-negative breast cancer cells are sensitive to PARP inhibitors used as radiosensitizers. Whether combining PARP inhibitors with radiotherapy in patients with triple-negative breast cancer would enhance the biological effectiveness of the irradiation and improve locoregional control is unclear, so the study, a phase 1 prospective dose-escalation trial, enrolled 24 patients with early-stage, high-risk triple-negative breast cancer to evaluate the safety profile of a concurrent administration of olaparib and radiotherapy, with overall survival and event-free survival as secondary outcomes. Olaparib therapy (administered orally at increasing doses from 50 to 200 mg twice daily) was started one week before radiotherapy and was then continued concomitantly with radiotherapy. No dose-limiting toxic effects were observed, and olaparib was escalated to 200 mg twice daily without reaching the maximum tolerated dose. No late treatment-related grade 3 or greater toxic effect was observed, and the maximum observed treatment-related toxic effects at the two-year follow-up were grade 2 breast pain and fibrosis. Three-year overall survival and event-free survival were 83% and 65% respectively. «The findings of this phase 1 dose-escalation trial suggest that PARP inhibition with olaparib concurrently with radiotherapy for early-stage, high-risk triple-negative breast cancer is well tolerated and should continue to be evaluated in further clinical trials«, authors conclude.
