Combination of Olaparib and radiotherapy for triple negative breast cancer: preliminary results of the RADIOPARP phase I trial.

Abstract Purpose Preclinical studies have evidenced that triple-negative breast cancer (TNBC) cell lines are more sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. This provides a strong rational for developing a new therapeutic approach for TNBC management based on PARP inhibition. The primary goal of the XXXXXXXXX phase-I trial was to evaluate the dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD) of Olaparib (O) combined with loco-regional radiotherapy (RT). Methods and Materials XXXXXXXXX was a single institutional phase I trial which evaluated Olaparib-radiotherapy combination in patients with inflammatory, locoregionally advanced or metastatic TNBC who received neoadjuvant chemotherapy. Radiotherapy delivered 50 Gy to the breast or to the chest wall. Lymph nodes could be included in target volumes according to local guidelines. The dose-finding toxicity-based study was conducted in sequential and adaptive Bayesian scheme with the method of Time-to-event Continual Reassessment, with four Olaparib dose levels (50mg, 100mg, 150mg and 200mg twice a day). Results Twenty-four patients with ECOG Performance Status of 0 or 1 were enrolled from September 2017 to November 2019. Twenty-one patients (87.5%) received the Olaparib-radiotherapy combination following breast surgery due to residual disease after neoadjuvant chemotherapy and the three other patients (12.5%) had unresectable tumors which were refractory to neo-adjuvant chemotherapy. All patients received full course combination treatment, as following: 4 patients (pts) at 50mgx2; 8 pts at 100mgx2; 7 pts at 150mgx2 and 5 pts at 200mgx2. No DLT was observed. Conclusion Olaparib was escalated to the maximum target dose of 200 mg twice a day without DLT. Further follow up is needed to evaluate the late toxicities. Pending the long-term results of the XXXXXXXXX trial, we suggest using Olaparib 200mg twice a day for future trials.