Abstract OT3-04-03: PARTNER randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients
Authors: Abraham J , Vallier A-L , Qian W , Grybowicz L , Thomas S , Machin A , Harvey C , Chiu E , McAdam K , Hughes-Davies L , Roylance R , Copson E , Armstrong A , Provenzano E , Tischkowitz M , McMurtry E , Earl H 
Published: February 2018

Abstract
Background: No specific targeted therapies are available for Triple Negative Breast Cancers (TNBC), an aggressive and diverse subgroup. The basal TNBC subgroup show some phenotypic and molecular similarities with germline BRCA (gBRCA). In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow drugs called PARP inhibitors (olaparib) to work more effectively.
Aims: To establish if the addition of olaparib to neoadjuvant platinum based chemotherapy for basal TNBC and/or gBRCA breast cancer is safe and improves efficacy (pathological complete response (pCR)).
Trial design: 3 stage open label randomised phase II/III trial of neoadjuvant paclitaxel and carboplatin +/olaparib, followed by clinicians' choice of anthracycline regimen.
Stage 1 and 2: Patients are randomised (1:1:1) to either control (3 weekly carboplatin AUC5/weekly paclitaxel 80mg/m2 for 4 cycles) or one of two research arms with the same chemotherapy regimen but with two different schedules of olaparib 150mg BD for 12 days.
Stage 3: Patients are randomised (1:1) to either control arm or to the research arm selected in stage 2.
Methods:
Stage 1 Safety: both research arms combined.
Stage 2 Schedule selection criteria: pCR rate and completion rate of olaparib protocol treatment. It is a “pickthewinner” design with 53 patients in each research arm. This allows a 90% power, 5% onesided significance level to test null hypothesis of pCR ≤35% versus an alternative hypothesis of pCR ≥55% in each of the research arms.
Stage 3 Efficacy:anticipated pCR ˜55-60% for all trial patients and ˜60-65% for gBRCA patients. The trial is powered to detect an absolute improvement of 15% (all patients) and 20% (gBRCA patients) by adding olaparib to chemotherapy (enriched design). TNBC patient recruitment will be capped, to ensure required gBRCA patients are enrolled. Enrichment design is applied with overall significance level 0.05(α) = 0.025(αall)+ 0.025(αgBRCA) and 80% power.
Target accrual: 527 [gBRCA 220] Current accrual: 56 Sites activated: 15 [expected number of sites 30-50].
Citation Format: Abraham J, Vallier A-L, Qian W, Grybowicz L, Thomas S, Machin A, Harvey C, Chiu E, McAdam K, Hughes-Davies L, Roylance R, Copson E, Armstrong A, Provenzano E, Tischkowitz M, McMurtry E, Earl H. PARTNER randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-04-03.