Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy Journal Article


Authors: Domchek, S. M.; Aghajanian, C.; Shapira-Frommer, R.; Schmutzler, R. K.; Audeh, M. W.; Friedlander, M.; Balmana, J.; Mitchell, G.; Fried, G.; Stemmer, S. M.; Hubert, A.; Rosengarten, O.; Loman, N.; Robertson, J. D.; Mann, H.; Kaufman, B.
Article Title: Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy
Abstract: Objective. The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCAI/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received >= 3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.gov NCT01078662) have been reported previously. Methods. Eligible patients were treated with oral olaparib 400 mg bid capsule monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for patients with measurable disease at baseline. Safety and tolerability were assessed for all patients by adverse event (AE) incidence and changes in laboratory parameters. Platinum resistance status was obtained retrospectively, and responses to olaparib evaluated. Results. In patients with gBRCA1/2m ovarian cancer, 154/193 (80%) had received >= 3 prior lines of chemotherapy, of whom 137/154 (89%) had measurable disease at baseline. ORR was 34% (46/137; 95% confidence interval [CI] 26-42) and median DoR was 7.9 (95% CI 5.6-9.6) months. ORR in platinum-resistant tumors was 30%. Median DoR for platinum-sensitive and platinum-resistant disease was similar: 8.2 months (95% CI 5.6-13.5) compared with 8.0 months (4.8-14.8), respectively. Six of the 193 (3%) patients had an AE with an outcome of death. None of these AEs at time of occurrence was considered causally related to olaparib. Conclusion. Following >= 3 prior lines of chemotherapy, olaparib 400 mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified. (C) 2016 Elsevier Inc. All rights reserved.
Keywords: ovarian cancer; carcinoma; phase ii; olaparib; platinum-based chemotherapy; trial; pegylated liposomal doxorubicin; multicenter; phase-2; poly(adp-ribose) polymerase; open-label; plus carboplatin; brcai/2 mutation
Journal Title: Gynecologic Oncology
Volume: 140
Issue: 2
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2016-02-01
Start Page: 199
End Page: 203
Language: English
ACCESSION: WOS:000369678900003
DOI: 10.1016/j.ygyno.2015.12.020
PROVIDER: wos
PUBMED: 26723501
PMCID: PMC4992984
Notes: Article -- Source: Wos
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