One-Year Toxicity Report of the RADIOPARP Phase I Trial Evaluating Olaparib With Radiotherapy for Triple Negative Breast Cancer.

Abstract

PURPOSE/OBJECTIVE(S)\nPreclinical studies have found that triple-negative breast cancer (TNBC) cells were sensitive to PARP1 inhibitors. The phase I dose-escalation RADIOPARP trial evaluated in TNBC patients the combination of breast radiotherapy and Olaparib, which was escalated to the target dose of 200 mg twice a day without dose-limiting toxicities. We report the one-year toxicity of this trial.\n\n\nMATERIALS/METHODS\nRADIOPARP is a monocentric prospective open-label phase I dose escalation trial evaluating the combination of breast radiotherapy and Olaparib in TNBC patients with inflammatory, locoregionally advanced or metastatic disease, or with residual disease after neoadjuvant chemotherapy. Olaparib was orally given at increasing dose levels (50mg, 100mg, 150mg or 200mg twice a day); radiotherapy consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation. One-year treatment-related toxicity was graded according to the CTCAE (version 4.03).\n\n\nRESULTS\nTwenty-four TNBC patients were enrolled between 09/2017 and 11/2019. Olaparib was escalated to 200 mg twice a day without dose-limiting toxicities. At one-year follow-up, no treatment-related grade ≥3 toxicity was observed (Table 1). Three patients had persistent grade 2 adverse events (breast pain, fibrosis and deformity); there were no cardiac, pulmonary or digestive toxicity.\n\n\nCONCLUSION\nThe one-year follow-up of the RADIOPARP phase I trial, evaluating breast radiotherapy with Olaparib in TNBC patients, demonstrated an acceptable toxicity profile of this combination with few low-grade adverse events.