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
Armstrong, Anne C
AffiliationUniversity of Cambridge, Cambridge
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AbstractBackground: No specific targeted therapies are available for triple negative breast cancer (TNBC), an aggressive and diverse subgroup. The basal TNBC subgroup show some phenotypic and molecular similarities with germline BRCA mutated BC (gBRCA). In gBRCA patients, and potentially other homologous recombination deficiencies, these already compromised pathways may allow PARP inhibitors to work more effectively. PARTNER was designed to establish if the addition of olaparib to neoadjuvant platinum-based chemotherapy for basal TNBC and/or gBRCA BC is safe and improves efficacy (pathological complete response (pCR)). Methods: Trial design: 3-Stage open label randomised Phase II/III trial of neoadjuvant CP: Carboplatin AUC5 with weekly Paclitaxel 80mg/m2 +/- olaparib 150mgBD for 12 days x 4 cycles, followed by clinicians' choice of anthracycline regimen x 3 cycles. Basal-TNBC and / or gBRCAm patients are eligible for inclusion. Tumour infiltrating lymphocytes and basal profile are assessed at baseline. Stage 1 and 2: Patients are randomised (1:1:1) to CP: CP + olaparib from day (D) –2: or CP + olaparib from D 3. Stage 3: Patients are randomised (1:1) to either control arm or to the research arm selected in stage 2. Primary end-points: Stage 1 – Safety; Stage 2 - Schedule selection criteria by pCR rate and completion rate of olaparib protocol treatment. 53 patients in each research arm will be evaluated within a “pick the winner” design. Null hypothesis of pCR ?35% versus alternative hypothesis of pCR ?55% will be tested with 90% power and 5% one sided significance level in each of the research arms. Stage 3 - Efficacy: anticipated pCR ~45-55% for all trial patients and ~50-60% 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). Enrichment design is applied with overall significance level 0.05(?) = 0.025(?all) + 0.025(?gBRCA) and 80% power. Current enrolment: 133 of planned 527 patients. Stage 1 accrual is complete. Stage 2 began in August 2017. 19 sites open and 12 more in active set-up. Clinical trial information: NCT03150576.
CitationAbraham J, Vallier AL, Qian W, Machin A, Grybowicz L, Thomas S, et al. Abstract OT3-03-03: 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. Cancer Res. 2019;79(4):OT3-03--OT3--.
TypeMeetings and Proceedings