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Gynecol Oncol. 2016 Feb;140(2):199-203. doi: 10.1016/j.ygyno.2015.12.020. Epub 2015 Dec 23.

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

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Basser Research Center and Abramson Cancer Center, Philadelphia, PA, USA. Electronic address:
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Sheba Medical Center, Tel Hashomer, Israel.
Center for Familial Breast and Ovarian Cancer and Center of Integrated Oncology, Cologne, Germany.
Samuel Oschin Cancer Institute, Los Angeles, CA, USA.
Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
Institute of Oncology, Rambam Health Care Campus, Haifa, Israel.
Rabin Medical Center, Petah Tikva, Israel.
Hadassah-Hebrew University Hospital Sharett Institute of Oncology, Jerusalem, Israel; Sharett Institute of Oncology, Jerusalem, Israel.
Shaare Zedek Medical Centre, Jerusalem, Israel.
Skånes universitetssjuk Lund, Lund, Sweden.
AstraZeneca, Macclesfield, UK.



The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.govNCT01078662) have been reported previously.


Eligible patients were treated with oral olaparib 400mg 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.


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: 8.2months (95% CI 5.6-13.5) compared with 8.0months (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.


Following ≥3 prior lines of chemotherapy, olaparib 400mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified.


BRCA1/2 mutation; Olaparib; Ovarian cancer; Phase II

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflicts of interestSM Domchek has received research funding from AbbVie, AstraZeneca and Clovis Oncology; C Aghajanian has received honoraria from AstraZeneca, and has received travel allowance and acted in an advisory/consulting role for AbbVie; RK Schmutzler has acted in an advisory/consulting role, and has received honoraria and research funding from AstraZeneca; MW Audeh, M Friedlander, G Fried, SM Stemmer, A Hubert and B Kaufman have received research funding from AstraZeneca; J Balmaña has received honoraria and research funding, and acted in an advisory/consulting role for AstraZeneca; G Mitchell and O Rosengarten have acted in an advisory/consulting role for Astra Zeneca and have received research funding from AbbVie and AstraZeneca; JD Robertson and Helen Mann were employees and held stock in AstraZeneca at the time of the study.R Shapira-Frommer and N Loman declare no conflict of interest.

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