التفاصيل البيبلوغرافية
| العنوان: |
Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study). |
| المؤلفون: |
Fasching, P.A.1, Link, T.1,2, Hauke, J.3, Seither, F.4, Jackisch, C.5, Klare, P.6, Schmatloch, S.7, Hanusch, C.8, Huober, J.9, Stefek, A.10, Seiler, S.4, Schmitt, W.D.11, Uleer, C.12, Doering, G.13, Rhiem, K.3, Schneeweiss, A.14, Engels, K.15, Denkert, C.16, Schmutzler, R.K.3, Hahnen, E.3 |
| المصدر: |
Annals of Oncology. Jan2021, Vol. 32 Issue 1, p49-57. 9p. |
| مصطلحات موضوعية: |
*COMBINATION drug therapy, *DRUG efficacy, *PACLITAXEL, *BREAST cancer treatment, *HER2 gene, *BRCA genes, *CANCER genetics |
| مستخلص: |
The efficacy and toxicity of olaparib as combination therapy in early breast cancer (BC) patients with homologous recombinant deficiency (HRD) [score high and/or germline (g) or tumour (t) BRCA1/2 mutation] is not well described. GeparOLA (ClinicalTrials.gov , NCT02789332) investigated olaparib in combination with paclitaxel in HER2-negative early BC with HRD. Patients with untreated primary HER2-negative cT2-cT4a-d or cT1c with either cN+ or pNSLN+ or cT1c and triple-negative breast cancer (TNBC) or cT1c and Ki-67>20% BC with HRD were randomised either to paclitaxel (P) 80 mg/m2 weekly plus olaparib (O) 100 mg twice daily for 12 weeks or P plus carboplatinum (Cb) area under the curve 2 weekly for 12 weeks, both followed by epirubicin/cyclophosphamide (EC). Stratification factors were hormone receptor (HR) status (HR+ versus HR−) and age (<40 versus ≥40 years). The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). A two-sided one-group χ2-test was planned to exclude a pCR rate of ≤55% in the PO-EC arm. Secondary end points were other pCR definitions, breast conservation rate, clinical/imaging response, tolerability and safety. A total of 107 patients were randomised between September 2016 and July 2018; 106 (PO N = 69; PCb N = 37) started treatment. Median age was 47.0 years (range 25.0-71.0); 36.2% had cT1, 61.0% cT2, 2.9% cT3, and 31.8% cN-positive tumours; grade 3 tumours: 86.8%; Ki-67>20%: 89.6%; TNBC: 72.6%; confirmed g BRCA1/2 mutation: 56.2%. The pCR rate with PO was 55.1% [90% confidence interval (CI) 44.5% to 65.3%] versus PCb 48.6% (90% CI 34.3% to 63.2%). Analysis for the stratified subgroups showed higher pCR rates with PO in the cohorts of patients <40 years and HR+ patients. GeparOLA could not exclude a pCR rate of ≤55% in the PO arm. PO was significantly better tolerated and the combination merits further evaluation. • Randomised phase II GeparOLA study investigated olaparib plus paclitaxel (PO) in early HER2-negative HRD breast cancer. • Addition of olaparib to chemotherapy could not exclude pCR ≤55% but was significantly better tolerated than carboplatinum. • Stratified subgroup analysis shows higher pCR rates with PO in cohorts <40 years and those with HR-positive tumours. • Overall, pCR rate in the g BRCA1/2 carriers was significantly higher than in non-carriers. • Combination of olaparib with paclitaxel prompts further investigation of olaparib as part of NACT in primary HRD tumours. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
Full Text Finder