Abstract 200P
Background
Following the introduction of olaparib into the early and mBC settings, there have been questions about optimal sequencing and decision-making between olaparib and capecitabine. While there are no data to support decisions in the early setting, the phase III randomised OlympiAD trial (NCT02000622) showed significantly longer PFS with olaparib vs single-agent chemotherapy of the physician’s choice (TPC; capecitabine, eribulin, or vinorelbine), in patients with gBRCAm HER2-negative mBC who had received ≤2 previous chemotherapy regimens for metastatic disease (Table). We report an exploratory post-hoc analysis of OlympiAD comparing the efficacy of olaparib vs capecitabine from the primary analysis (data cut-off 9 Dec 2016).
Methods
Patients were randomised to olaparib 300 mg twice daily (n=205) or TPC (n=97; of which n=43 received capecitabine 2500 mg/m2 for 14 days every 21 days). Analyses were conducted in all patients and those with triple-negative BC (TNBC). Post-hoc analyses compared olaparib vs capecitabine in capecitabine-eligible patients (i.e., olaparib patients who would have received capecitabine if they had been randomised to TPC). The primary endpoint was PFS by blinded independent central review.
Results
In all analysed populations, olaparib was associated with improved median PFS vs TPC or capecitabine (Table). Safety was aligned with published data. Table: 200P
PFS by blinded independent central review
| Population | Olaparib | Comparator (TPC or capecitabine) | HR (95% CI) | |||
| Events n/N (%) | Median, months | Events n/N (%) | Median, months | |||
| All patients | Olaparib vs TPC | 163/205 (79.5) | 7.0 | 71/97 (73.2) | 4.2 | 0.58 (0.43–0.80); p=0.0009* |
| Capecitabine-eligible patient subgroup: Olaparib vs capecitabine | 72/95 (75.8) | 8.2 | 32/43 (74.4) | 4.2 | 0.55 (0.34–0.89) | |
| Patients with TNBC | Olaparib vs TPC | 81/102 (79.4) | 5.6 | 40/48 (83.3) | 2.9 | 0.43 (0.29–0.63) |
| Capecitabine-eligible patient subgroup: Olaparib vs capecitabine | 34/44 (77.3) | 5.9 | 20/23 (87.0) | 2.9 | 0.32 (0.16– 0.64) |
∗OlympiAD was powered to assess the PFS benefit between olaparib vs TPC in this population.
Conclusions
Olaparib was associated with longer PFS vs TPC or capecitabine with an acceptable safety profile in gBRCAm HER2-negative mBC. These results may aid in the optimal treatment selection for patients with gBRCAm BC. Limitations included the exploratory nature of the analysis and small sample sizes.
Clinical trial identification
NCT02000622.
Editorial acknowledgement
Writing and editorial assistance was provided by Sara Shaw PhD, CMPP of BOLDSCIENCE Inc., funded by AstraZeneca and MSD.
Legal entity responsible for the study
AstraZeneca.
Funding
This study was supported by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who are codeveloping olaparib (MSD).
Disclosure
M. Robson: Financial Interests, Personal, Other, Review guideline pathways: Change Healthcare; Financial Interests, Personal, Invited Speaker, Speaker at CME events (NOT speaker's bureau): Physician's Education Resource, Research to Practice, Intellisphere, MJH Holdings; Financial Interests, Personal, Advisory Board, Speaker at CME events (NOT speaker's bureau): MyMedEd; Financial Interests, Institutional, Invited Speaker, Funding for research study (ICEBERG, dating to 2007): AstraZeneca; Financial Interests, Personal, Invited Speaker, Steering Committee Member for CAPITELLO-290, uncompensated: AstraZeneca; Financial Interests, Institutional, Other, Co-PI for Merck IIT of neoadjuvant olaparib/pembrolizumab in BRCA carriers, no personal compensation: Merck; Financial Interests, Personal, Invited Speaker, Steering Committee member for KEYLNK-009, no compensation: Merck; Financial Interests, Institutional, Invited Speaker, Local PI of KEYLNK009: Merck; Financial Interests, Institutional, Other, Local co-PI of clinical trial of ZEN03694 and talazoparib in TNBC, no personal compensation: Pfizer; Non-Financial Interests, Advisory Role: Zenith Pharmaceuticals, Epic Biosciences, Daiichi Sankyo, Tempus Labs; Non-Financial Interests, Personal, Other, Editorial services for writing of reports for ABRAZO clinical trial: Pfizer; Non-Financial Interests, Personal, Other, Editorial services for medical writing of reports resulting from OlympiAD trial: AstraZeneca; Non-Financial Interests, Member: ASCO. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre Fabre, Orion, Sanofi, Rappta, Cellectis, Isis/servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, AstraZeneca, Orion, Sanofi, Pfizer; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker, ESMO symposium: Gilead; Financial Interests, Institutional, Advisory Board, scientific board: Elsan; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM; Non-Financial Interests, Principal Investigator, H2020 funding: European Commission. S.M. Domchek: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Clovis Oncology, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: AstraZeneca, Clovis Oncology. P.F. Conte: Financial Interests, Personal, Advisory Board, advisory board for alpelisb trial: Novartis; Financial Interests, Institutional, Research Grant: merch Kga. S. Im: Financial Interests, Personal, Advisory Board, No payment: AstraZeneca, Bertis, Daiichi Sankyo, Eisai, GSK, Hanmi, Lilly, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal and Institutional, Principal Investigator, Clinical trial budget: AstraZeneca, Daiichi Sankyo, Eisai, Hanmi, Lilly, MSD, Novartis, Pfizer, Roche; Financial Interests, Institutional, Research Grant, Clinical trial budget: AstraZeneca, Boryung Pharm; Financial Interests, Institutional, Research Grant: Dae Woong, Eisai, Pfizer, Roche; Financial Interests, Personal, Advisory Board: Idience. B. Xu: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer, Roche; Financial Interests, Institutional, Research Grant: Henrui. A. Armstrong: Financial Interests, Personal, Advisory Board: Gilead Sciences, MSD; Financial Interests, Personal, Other, Travel, accommodation, expenses: Gilead Sciences, MSD Oncology, Novartis; Financial Interests, Personal, Stocks/Shares, Owned by immediate family member: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune. N. Masuda: Financial Interests, Personal, Invited Speaker: Chugai, AstraZeneca, Eisai, Eli Lilly, Pfizer, Dai-ichi Sankyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa-Kirin, MSD, Novartis, Pfizer, Sanofi, Ono Pharma; Non-Financial Interests, Invited Speaker: Japan Breast Cancer Research Group, Japanese Breast Cancer Society. R. Hettle: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Fielding: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N.M. Tung: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca. E. Senkus-Konefka: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Cancérodigest, Eli Lilly, Gilead, high5md, Novartis, Pfizer, MSD; Financial Interests, Personal, Other, commenting on scientific meeting in social media: Curio Science; Financial Interests, Personal, Other, travel expenses: Gilead, Egis, Novartis, Roche; Financial Interests, Personal, Stocks/Shares: AstraZeneca, Eli Lilly, Pfizer; Financial Interests, Personal, Royalties: Springer; Financial Interests, Personal and Institutional, Invited Speaker: Amgen, Eli Lilly, Novartis, OBI Pharma, Samsung; Financial Interests, Personal and Institutional, Other, SI: AstraZeneca, Roche, Pfizer.