GeparOLA: A randomized phase II trial to assess the efficacy of paclitaxel and olaparib in comparison to paclitaxel/carboplatin followed by epirubicin/cyclophosphamide as neoadjuvant chemotherapy in patients (pts) with HER2-negative early breast cancer (BC) and homologous recombination deficiency (HRD)

Autor: Peter A. Fasching, Christian Jackisch, Kerstin Rhiem, Andreas Schneeweiss, Peter Klare, Claus Hanusch, Jens Bodo Huober, Theresa Link, Michael Untch, Sabine Schmatloch, Carsten Denkert, Andrea Stefek, Christoph Uleer, Gabriele Doering, Knut Engels, Fenja Seither, Jens Uwe Blohmer, Sibylle Loibl
Rok vydání: 2019
Předmět:
Zdroj: Journal of Clinical Oncology. 37:506-506
ISSN: 1527-7755
0732-183X
Popis: 506 Background: The efficacy and toxicity of olaparib in early BC pts with homologous DNA repair deficiency (here defined as HRD score high tumors +/- germline (g) or tumor (t) BRCA mutation) is not well described. GeparOLA investigates olaparib in HER2 negative early BC with HRD. Methods: GeparOLA (NCT02789332) randomized 102 pts to either paclitaxel 80 mg/m² weekly (Pw) plus olaparib 100 mg twice daily for 12 weeks (PwO n = 65) or Pw plus carboplatin (Cb) AUC2 weekly for 12 weeks (PwCb n = 37), both followed by EC. Randomization was stratified by hormone receptor-status (HR+ vs HR-) and age ( < 40 vs ≥40 years). Pts with untreated primary cT2 - cT4a-d or cT1c with either cN+ or pNSLN+ or triple negative or Ki-67 > 20% were included, with either g/t BRCA mutation and/or high HRD score. The primary endpoint is pathological complete response (pCR; ypT0/is ypN0). A one group χ2-test was planned to exclude the pCR rate of ≤55% in PwO→EC arm. Secondary endpoints are other pCR definitions, breast conservation rate, clinical and imaging response, tolerability and safety. Results: A total of 107 pts were randomized between 9/2016 and 7/2018; 106 started treatment. Median age was 47.0 years [range 25.0-71.0]; 36.2% of pts had cT1, 61.0% cT2, 2.9% cT3, and 31.8% cN-positive tumors; G3: 86.8%; Ki-67 > 20%: 89.6%; TNBC 72.6%; confirmed g /tBRCA 1/2 mutation: 60.4%. pCR rate with PwO was 55.1% (90%CI 44.5%-65.3%) vs PwCb 48.6% (90%CI 34.3%-63.2%). Analysis for the stratified subgroups showed higher pCR rates with PwO in the cohorts of pts < 40 years and HR+ pts Clinical trial information: NCT02789332. Conclusions: GeparOla could not exclude a pCR rate of ≤55% in the PwO arm. Subgroup analysis is hypothesis generating and need further confirmation.[Table: see text]
Databáze: OpenAIRE
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