Abstract AS28: Phase Ib/II with expansion of patients at the mtd study of olaparib plus weekly (metronomic) carboplatin and paclitaxel in relapsed ovarian cancer

Abstract BACKGROUND: To establish the maximum-tolerated dose (MTD) and evaluate dose-limiting toxicities (DLTs) and response to therapy of combination therapy with carboplatin/paclitaxel and olaparib, an oral tablet inhibitor of poly ADP ribose polymerase (PARP), in advanced (Stage III or IV) relapsed ovarian cancer. METHODS: Eligibility required measurable disease, adequate organ function and ECOG performance status of ≤ 2. Patients had to have failed first line platinum containing chemotherapy. All patients were tested for BRCA 1 and 2 mutations. Patients received the metronomic therapy of paclitaxel 60mg/m2 IV and carboplatin AUC 2 IV weekly, 3 weeks out of 4 and increasing doses of olaparib until the maximum tolerated dose was obtained. Olaparib started at 50 mg bid administered orally for 3 consecutive days (D1-D3), every week for each cycle. Patients were assessed for toxicity and response according to the protocol. Patients received combination therapy until DLT or disease progression. RESULTS: The maximum tolerated dose was found to be olaparib 150 mg bid administered orally, three (D1-D3) consecutive days of each week of each cycle. Total number of patients enrolled in the phase 1b part of this study was 14. Median age was 58 (range 42-77). The median number of prior therapeutic regimens was 4 (range 3-8). Median number of cycles on study to date is 9.3 and the mean is 7.3. There were no grade 4 toxicities. The most common grade 3 toxicities were neutropenia (11), leukopenia (7), lymphopenia (4), anemia (4), fatigue (1) and MDS (1). There was no evidence of GI, cardiac, hepatic, pulmonary or dermatologic toxicities in any of these patients. Two patients had an allergic reaction prior to participating in the trial and once enrolled were desensitized to carboplatin for each study visit. One patient had a mild allergic reaction to the chemotherapy on trial, but did not require desensitization. 4 patients had a complete response (CR), 3 had partial response (PR), 3 had stable disease (SD), 2 had progressive disease (PD) and 2 were not evaluable. Of the 4 CR's three were BRCA mutant and 1 had no known BRCA mutation. Of the PD's one was BRCA mutant. CONCLUSION: Olaparib, an oral tablet can be safely administered with a weekly regimen of carboplatin and paclitaxel in heavily pretreated, ovarian cancer patients. This is early preliminary data. This study is ongoing with a planned total expansion of 40 additional patients at the MTD. Citation Format: Rivkin SE, Iriarte D, Sloan, H, Wiseman, C, Moon J,. Phase Ib/II with expansion of patients at the mtd study of olaparib plus weekly (metronomic) carboplatin and paclitaxel in relapsed ovarian cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS28.