Olaparib (O) in patients (pts) with prostate cancer with BRCA1/2 inactivating mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

Abstract

5567 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Advanced prostate cancer (PC) pts with germline or somatic BRCA1/2 inactivating mutations treated with O are reported. Methods: Eligible pts had advanced PC, no remaining standard treatment (tx) options, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Tumor genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received O tablets or capsules dosed at 300 mg (n=24) or 400 mg (n=5), respectively, orally twice daily until disease progression. Simon 2-stage design tested the null disease control (DC) (objective response (OR) or stable disease at 16+ weeks (wks) (SD16+) according to RECIST) rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Pts had radiographic evaluations at 8 and 16 wks and then every 12 wks. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts with BRCA1/2 inactivating mutations were enrolled from Aug 2016 to Jul 2019; 4 were identified as ineligible after enrollment due to bone only disease and removed from analyses. Demographics and investigator-reported outcomes are summarized in the Table. Nine pts with OR and 8 with SD16+ were observed for DC and OR rates of 68% (90% CI: 53% - 77%) and 36% (95% CI: 18% - 57%), respectively. Six pts had at least one grade 3 AE or SAE at least possibly related to O including anemia, aspiration, dehydration, diabetic ketoacidosis, fatigue, and neutropenia. Conclusions: Monotherapy with O showed anti-tumor activity in heavily pre-treated PC pts with germline (1/2 pts with OR or SD16+) or somatic (16/23 pts with OR or SD16+) BRCA1/2 inactivating mutations. These findings extend results from recent trials of O in advanced prostate cancer pts with germline only BRCA1/2 mutations. Clinical trial information: NCT02693535 . [Table: see text]