331TiP - OlympiA, Neo-Olympia and OlympiAD: Randomized Phase III trials of olaparib in patients (pts) with breast cancer (BC) and a germline BRCA1/2 mutatio...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Pathology/Molecular Biology
Presenter Andrew Tutt
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors A. Tutt1, J. Balmana2, M. Robson3, J. Garber4, B. Kaufman5, C. Geyer6, K. Saini7, M. Stuart8, H. Mann8, P.A. Fasching9
  • 1Breakthrough Breast Cancer Research Unit, King's College London Guy's Hospital, SE1 9RT - London/GB
  • 2Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 3., Memorial Sloan-Kettering Cancer Center, New York/US
  • 4., Dana Farber Cancer Institute, Boston/US
  • 5Division Of Oncology, Sheba Medical Center, IL-52621 - Tel Hashomer/IL
  • 6Massey Cancer Center, Virginia Commonwealth University, Richmond/US
  • 7Jules Bordet Institute, Breast International Group (BIG), Brussels/BE
  • 8., AstraZeneca, Macclesfield/GB
  • 9., University Hospital Erlangen and German Breast Group, Erlangen and Neu Isenburg/DE

Abstract

Background

A Phase II study (NCT00494234) showed that the oral PARP inhibitor olaparib (400 mg bid; capsules) exerts antitumour activity in BC pts with a gBRCAm (Tutt et al Lancet 2010). Three Phase III trials of olaparib monotherapy have been initiated in BC pts with a gBRCAm: OlympiA (NCT02032823), Neo-Olympia (D081EC00005), OlympiAD (NCT02000622).

Trial design

Trial designs are summarized in the Table. For each trial, eligible pts will have a BRCAm and will undergo gBRCAm testing (Myriad Integrated BRACAnalysis®) as part of the trial. For OlympiA, pts must be at high risk of recurrence and have completed local treatment and either neoadjuvant (without pCR) or adjuvant chemotherapy. For Neo-Olympia, pts can have operable, locally advanced or inflammatory BC, must have a tumour >2 cm by clinical exam (or >1 cm by radiological exam) and must have completed four cycles of anthracycline plus carboplatin without disease progression. For OlympiAD, pts can have TNBC or HER2-negative BC, and must have received prior anthracycline and taxane in the adjuvant or metastatic setting, and ≤2 chemotherapy lines for mBC. In OlympiA, pts will receive treatment for up to 12 months; efficacy will be assessed q 3 months up to 24 months, then q 6 months up to 60 months, then q 12 months. In Neo-Olympia, pts will receive treatment for 12 wks pre-surgery and then for 40 wks post-surgery. In OlympiAD, PFS will be assessed by RECIST v1.1; radiologic exams will be performed at baseline, q 6 wks up to 6 months, and then q 12 wks until disease progression. In OlympiA and OlympiAD, IDFS and PFS, respectively, will be analyzed using stratified log-rank tests; for Neo-Olympia, pCR rate will be analyzed with an adjusted logistic regression model. Primary analyses will be undertaken after 330 IDFS events (OlympiA), surgery (Neo-Olympia) and 230 PFS events (OlympiAD). Enrolment began in March 2014 for OlympiAD, April 2014 for OlympiA and is expected to begin in Q3 2014 for Neo-Olympia.

OlympiA Neo-Olympia OlympiAD
Setting Adjuvant treatment for high-risk, primary TNBC Neo-adjuvant treatment for primary TNBC Metastatic BC (mBC)
Design Randomized (1:1), double-blind, parallel-group Randomized (1:1:1), three-arm, parallel-group Randomized (2:1), open-label
Olaparib monotherapy arm 300 mg bid (tablet) 300 mg bid (tablet) (Arm A)* 300 mg bid (tablet)
Comparator arm(s) Placebo Placebo + weekly paclitaxel 80 mg/m2 for 12 wks (Arm B)* Physician's choice of capecitabine 2500 mg/m2 (d1-14 q 21d), vinorelbine 30 mg/m2 (d1, d8 q 21d) or eribulin 1.4 mg/m2 (d1, d8 q 21d)
Olaparib 100 mg bid (tablet) + weekly paclitaxel 80 mg/m2 for 12 wks (Arm C)*
Primary endpoint IDFS pCR rate PFS (BICR)
Secondary endpoints OS, DDFS, incidence of new cancers OS, EFS, DDFS, ORR at 12 wks OS, PFS2, ORR
HRQoL HRQoL HRQoL
Other objectives Safety, tolerability Safety, tolerability Safety, tolerability
Target recruitment (pts) 1320 300 310

*Curative-intent surgery to be performed after 12 wks, after which pts will receive olaparib 300 mg bid (Arm A), placebo (Arm B), or either weekly paclitaxel 80 mg/m2 for 12 wks (followed by olaparib 300 mg bid) or olaparib 300 mg bid (Arm C) BICR, blinded independent central review; d, days; DDFS, distant disease-free survival; EFS, event-free survival; IDFS, invasive disease-free survival; ORR, objective response rate; OS, overall survival; pCR, pathological complete response; PFS, progression-free survival; q, every; PFS2, time to second disease progression or death; TNBC, triple-negative breast cancer; wks, weeks

Disclosure

J. Garber: Research funding – Myriad; M. Stuart: AZ employee and owns stock in AZ; H. Mann: AZ employee and owns stock in AZ. All other authors have declared no conflicts of interest.