PMID- 30689707
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20240229
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 30
IP  - 4
DP  - 2019 Apr 1
TI  - OlympiAD final overall survival and tolerability results: Olaparib versus 
      chemotherapy treatment of physician's choice in patients with a germline BRCA 
      mutation and HER2-negative metastatic breast cancer.
PG  - 558-566
LID - S0923-7534(19)31111-1 [pii]
LID - 10.1093/annonc/mdz012 [doi]
AB  - BACKGROUND: In the OlympiAD study, olaparib was shown to improve progression-free 
      survival compared with chemotherapy treatment of physician's choice (TPC) in 
      patients with a germline BRCA1 and/or BRCA2 mutation (BRCAm) and human epidermal 
      growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). We now 
      report the planned final overall survival (OS) results, and describe the most 
      common adverse events (AEs) to better understand olaparib tolerability in this 
      population. PATIENTS AND METHODS: OlympiAD, a Phase III, randomized, controlled, 
      open-label study (NCT02000622), enrolled patients with a germline BRCAm and 
      HER2-negative mBC who had received </=2 lines of chemotherapy for mBC. Patients 
      were randomized to olaparib tablets (300 mg bid) or predeclared TPC 
      (capecitabine, vinorelbine, or eribulin). OS and safety were secondary end 
      points. RESULTS: A total of 205 patients were randomized to olaparib and 97 to 
      TPC. At 64% data maturity, median OS was 19.3 months with olaparib versus 
      17.1 months with TPC (HR 0.90, 95% CI 0.66-1.23; P = 0.513); median follow-up was 
      25.3 and 26.3 months, respectively. HR for OS with olaparib versus TPC in 
      prespecified subgroups were: prior chemotherapy for mBC [no (first-line setting): 
      0.51, 95% CI 0.29-0.90; yes (second/third-line): 1.13, 0.79-1.64]; receptor 
      status (triple negative: 0.93, 0.62-1.43; hormone receptor positive: 0.86, 
      0.55-1.36); prior platinum (yes: 0.83, 0.49-1.45; no: 0.91, 0.64-1.33). Adverse 
      events during olaparib treatment were generally low grade and manageable by 
      supportive treatment or dose modification. There was a low rate of treatment 
      discontinuation (4.9%), and the risk of developing anemia did not increase with 
      extended olaparib exposure. CONCLUSIONS: While there was no statistically 
      significant improvement in OS with olaparib compared to TPC, there was the 
      possibility of meaningful OS benefit among patients who had not received 
      chemotherapy for metastatic disease. Olaparib was generally well-tolerated, with 
      no evidence of cumulative toxicity during extended exposure. Please see the 
      article online for additional video content.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the 
      European Society for Medical Oncology.
FAU - Robson, M E
AU  - Robson ME
AD  - Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York. 
      Electronic address: robsonm@mskcc.org.
FAU - Tung, N
AU  - Tung N
AD  - Cancer Risk and Prevention Program, Beth Israel Deaconess Medical Center, 
      Department of Medicine, Dana-Farber Harvard Cancer Center, Boston, USA.
FAU - Conte, P
AU  - Conte P
AD  - Division of Oncology, University of Padova, Istituto Oncologico Veneto IRCCS, 
      Padova, Italy.
FAU - Im, S-A
AU  - Im SA
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University College of Medicine, Seoul, Korea.
FAU - Senkus, E
AU  - Senkus E
AD  - Center of Breast Diseases, Medical University of Gdansk, Gdansk, Poland.
FAU - Xu, B
AU  - Xu B
AD  - Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical 
      Sciences, Beijing, China.
FAU - Masuda, N
AU  - Masuda N
AD  - Department of Surgery, Osaka National Hospital, National Hospital Organization, 
      Osaka, Japan.
FAU - Delaloge, S
AU  - Delaloge S
AD  - Breast Oncology, Institut Gustave Roussy, Villejuif, France.
FAU - Li, W
AU  - Li W
AD  - Department of Emergency, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Armstrong, A
AU  - Armstrong A
AD  - Medical Oncology, Christie Hospital NHS Foundation Trust, Manchester, UK.
FAU - Wu, W
AU  - Wu W
AD  - Global Medicines Development, AstraZeneca, Gaithersburg, USA.
FAU - Goessl, C
AU  - Goessl C
AD  - Global Medicines Development, AstraZeneca, Gaithersburg, USA.
FAU - Runswick, S
AU  - Runswick S
AD  - Global Medicines Development, AstraZeneca, Macclesfield, UK.
FAU - Domchek, S M
AU  - Domchek SM
AD  - Department of Medicine, Basser Center, University of Pennsylvania, Philadelphia, 
      USA.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (BRCA1 Protein)
RN  - 0 (BRCA1 protein, human)
RN  - 0 (Phthalazines)
RN  - 0 (Piperazines)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 0 (Tablets)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - WOH1JD9AR8 (olaparib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Anemia/chemically induced/epidemiology
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - BRCA1 Protein/genetics
MH  - Breast Neoplasms/*drug therapy/genetics/mortality/pathology
MH  - Female
MH  - Follow-Up Studies
MH  - Germ-Line Mutation
MH  - Humans
MH  - Middle Aged
MH  - Phthalazines/*administration & dosage/adverse effects
MH  - Piperazines/*administration & dosage/adverse effects
MH  - Poly(ADP-ribose) Polymerase Inhibitors/*administration & dosage/adverse effects
MH  - Progression-Free Survival
MH  - Receptor, ErbB-2/analysis/metabolism
MH  - Tablets
PMC - PMC6503629
OTO - NOTNLM
OT  - PARP inhibitor
OT  - breast cancer
OT  - germline BRCA mutation
OT  - olaparib
OT  - overall survival
OT  - tolerability
EDAT- 2019/01/29 06:00
MHDA- 2020/04/21 06:00
PMCR- 2019/01/23
CRDT- 2019/01/29 06:00
PHST- 2019/01/29 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
PHST- 2019/01/29 06:00 [entrez]
PHST- 2019/01/23 00:00 [pmc-release]
AID - S0923-7534(19)31111-1 [pii]
AID - mdz012 [pii]
AID - 10.1093/annonc/mdz012 [doi]
PST - ppublish
SO  - Ann Oncol. 2019 Apr 1;30(4):558-566. doi: 10.1093/annonc/mdz012.