Half-dose olaparib reduction: Safe and efficient dose in multi-treated Mexican ovarian cancer patients.

Abstract

e17101 Background: Ovarian cancer (OC) is the most common gynecological cancer worldwide, and in Mexico stands as the 2nd gynecological cancer-related death cause with 4,759 new cases yearly. PARP inhibitors in BRCA1/2 mutated patients offer disease control after response to chemotherapy with few side effects and minimal impact on quality of life. The primary objective of this study was to evaluate the clinical benefit of Olaparib half-dose reduction in multi-treated Mexican OC patients. Methods: Nineteen OC BRCA1/2 positive patients were enrolled (Nov 2016-Dec 2018), at the Instituto Nacional de Cancerología, Mexico. Eligible patients had received > 2 previous platinum-based lines. Olaparib dose was 800 mg/day, as maintenance therapy after complete or partial response. Half-dose administration was allowed in grade 3 toxicity events. Median PFS curves were estimated by the Kaplan–Meier method. Results: The most common mutation in OC patients was BRCA1 (78.9%), four patients had founder mutation (Del9-12). Eleven patients (57.9%) received Olaparib in ≥4 lines. Nine patients required dose adjustment following hematological (42.1%) and gastrointestinal toxicity (5.2%). There was not statistical differences between complete-dose and half-dose administration groups. However patients with founder BRCA1 mutation did not require dose adjustment ( P= 0.033) and multi-treated (≥4 lines) patients were more susceptible to develop hematological toxicity ( P= 0.030). The median PFS was 12.02 months, patients HGSP histology had a better PFS compared with endometroid histology (14.8 Vs 5.19; P= 0.020). BRCA1 founder mutated patients had a better PFS compared with other BRCA mutations (NR Vs 11.30; P= 0.050). The median PFS in first, second and third or more recurrence was NR Vs 14.8 Vs 8.3; P= 0.050. We did not find statistical difference in the PFS in half-dose reduction compared with complete-dose groups (9.6 Vs NR; P= 0.221). Conclusions: We provide evidence that using Olaparib in first and second recurrence had better outcome compared with third or more recurrence. However the recommended dose exhibits a high toxicity profile; therefore half-dose reduction in multi-treated patients needs to be suggested in Olaparib OC guidelines as a safety and effective strategy.