Abstract OT1-1-04: OlympiA, Neo-Olympia and OlympiAD: Randomized phase III trials of olaparib in patients (pts) with breast cancer (BC) and a germline <i>BRCA1/2</i> mutation (gBRCAm)
Authors: Mark Robson, Andrew Tutt, Judith Balmaña, Bella Kaufman, Judy Garber, Charles Geyer, James Ford, Priyanka Sharma, Mary Stuart, Helen Mann, Peter A Fasching
Journal: Cancer Research (2015)

Abstract Background A Phase II study showed that the PARP inhibitor olaparib (400 mg bid; capsules) exerts antitumor 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 OlympiANeo-OlympiaOlympiADSettingAdjuvant therapy for high-risk, primary TNBCNeo-adjuvant therapy for primary TNBCMetastatic BC (mBC)DesignRandomized (1:1), double-blind, parallel-groupRandomized (1:1:1), three-arm, parallel-groupRandomized (2:1), open-labelOlaparib monotherapy arm300 mg bid (tablet)300 mg bid (tablet) (Arm A)*300 mg bid (tablet)Comparator arm(s)PlaceboPlacebo + weekly paclitaxel 80 mg/m2 for 12 wks (Arm B)* Olaparib 100 mg bid (tablet) + weekly paclitaxel 80 mg/m2 for 12 wks (Arm C)*Physician's choice of capecitabine 2500 mg/m2 (d1-14 q21d), vinorelbine 30 mg/m2 (d1, d8 q21d) or eribulin 1.4 mg/m2 (d1, d8 q21d)Primary endpointIDFSpCR ratePFS (BICR)Secondary endpointsOS, DDFS, incidence of new cancersOS, EFS, DDFS, ORR at 12 wksOS, PFS2, ORR HRQoLHRQoLHRQoLOther objectivesSafety, tolerabilitySafety, tolerabilitySafety, tolerabilityTarget recruitment (pts)1320300310*Curative-intent surgery to be performed after 12 wks; pts will then receive olaparib 300 mg bid (Arm A), placebo (Arm B), or either weekly paclitaxel 80 mg/m2 for 12 wks (then 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; pCR, pathological complete response; q, every; PFS2, time to second disease progression or death; TNBC, triple-negative BC 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. Neo-Olympia pts can have operable, locally advanced or inflammatory BC, must have a tumor &amp;gt;2cm by clinical exam (or &amp;gt;1cm by radiological exam) and have completed four cycles of anthracycline plus carboplatin without progression. OlympiAD pts can have TNBC or HER2– BC, and must have received prior anthracycline and taxane in the adjuvant or metastatic setting, and ≤2 chemotherapy lines for mBC. OlympiA pts will be treated for up to 12 months (m); efficacy will be assessed q3m up to 24m, then q6m up to 60m, then q12m. Neo-Olympia pts will be treated for 12 wks (w) pre-surgery, then for 40w post-surgery. In OlympiAD, PFS will be assessed by RECIST v1.1; radiologic exams will be performed at baseline, q6w up to 6m, then q12w until progression. In OlympiA and OlympiAD, IDFS and PFS 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). Enrollment began in Mar 2014 for OlympiAD, Apr 2014 for OlympiA and is expected to begin in Q3 2014 for Neo-Olympia. Citation Format: Mark Robson, Andrew Tutt, Judith Balmaña, Bella Kaufman, Judy Garber, Charles Geyer, James Ford, Priyanka Sharma, Mary Stuart, Helen Mann, Peter A Fasching. OlympiA, Neo-Olympia and OlympiAD: Randomized phase III trials of olaparib in patients (pts) with breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-1-04.