The Phase III OlympiAD study (NCT02000622) in patients with metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm) showed a statistically significant progression-free survival (PFS) benefit for olaparib monotherapy over chemotherapy treatment of physician’s choice (TPC; hazard ratio [HR] 0.58; 95% CI 0.43, 0.80; P
OlympiAD was a randomized, open-label, Phase III study of olaparib monotherapy vs TPC in HER2-negative mBC patients with a gBRCAm who had received ≤2 chemotherapy lines in the metastatic setting. Patients were randomized 2:1 to olaparib tablets (300 mg bid) or single-agent TPC (capecitabine, eribulin or vinorelbine). Patients had ≥1 lesion suitable for assessments according to modified RECIST 1.1. The primary endpoint was PFS by blinded independent central review.
302 patients were randomized to olaparib (n = 205) or TPC (n = 97). In patients with measurable disease, objective response rate (ORR) was 59.9% for olaparib patients (n = 167; complete response [CR] 9.0%, partial response [PR] 50.9%, stable disease ≥5 weeks [SD] 25.1%; progressive disease [PD] 15.0%) and 28.8% for TPC patients (n = 66; CR 1.5%, PR 27.3%, SD 37.9%, PD 33.3%). Median best percentage change from baseline in target lesion size was −45.1% for olaparib and −14.8% for TPC.
Olaparib monotherapy in OlympiAD led to a doubling of ORR vs TPC and a larger reduction in target lesion size, indicating a more pronounced depth of response in HER2-negative gBRCAm mBC patients. PFS was longer with olaparib than with TPC, irrespective of tumour burden and location.
Clinical trial identification
NCT02000622, 15 June 2017
Legal entity responsible for the study
S. Delaloge: Honoraria, research funding, consulting, and travel, expenses and accommodation from Novartis, Roche, AstraZeneca, Pfizer, GE Healthcare, and Puma Biotechnology. P.F. Conte: Speakers’ bureau with Roche-Genentech, Novartis, AstraZeneca and Lilly, travel, accommodations, and expenses from Novartis, Celgene and AstraZeneca, and research funding from Roche, Novartis and Merck Serono. S-A. Im: Consultancy for Novartis, Hanmi and Spectrum Pharmaceuticals. E. Senkus-Konefka: Honoraria from Amgen, AstraZeneca, Pfizer, Pierre Fabre and Roche, and consulting for Amgen, AstraZeneca, Pfizer, Pierre Fabre and Roche. S.M. Domchek: Research funding to the University of Pennsylvania from AstraZeneca, Clovis Oncology, AbbVie and Pharmamar. N. Masuda: Honoraria from Chugai Pharma, AstraZeneca and Kyowa Hakko Kirin, and research funding from Chugai Pharma, AstraZeneca, Kyowa Hakka Kirin, MSD, Novartis, Pfizer and Lilly. N. Tung: Patents, royalties and other intellectual property with Ambry Genetics, and research funding from Myriad Genetics. A. Armstrong: Consulting for Roche and Syndax. W. Wu, C. Goessl, S. Runswick: Employee of and stock ownership in AstraZeneca. M. Robson: Consultancy for AstraZeneca and McKesson, travel, accommodation and expenses from AstraZeneca, honoraria from AstraZeneca and research funding from AstraZeneca, AbbVie, Myriad Genetics and Medivation. All other authors have declared no conflicts of interest.\r\nTable 243PD
Subgroup analyses for PFS by baseline tumour burden and location are shown in the Table.\r\n
|\r\n||Olaparib 300 mg bid\r\n||Chemotherapy TPC\r\n|
|1 metastatic site, n\r\n||46\r\n||25\r\n|
|Median PFS, months\r\n||8.4\r\n||4.2\r\n|
|HR (95% CI)\r\n||0.62 (0.35, 1.13)\r\n|
|≥2 metastatic sites, n\r\n||159\r\n||72\r\n|
|Median PFS, months\r\n||6.5\r\n||3.0\r\n|
|HR (95% CI)\r\n||0.59 (0.43, 0.82)\r\n|
|Bone-only metastases, n\r\n||16\r\n||6\r\n|
|Median PFS, months\r\n||11.2\r\n||–\r\n|
|HR (95% CI)\r\n||Not calculated\r\n|
|Other metastatic sites,* n\r\n||189\r\n||91\r\n|
|Median PFS, months\r\n||6.6\r\n||3.9\r\n|
|HR (95% CI)\r\n||0.60 (0.46, 0.81)\r\n|
Includes both bone and other tumour locations\r\n