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Neoadjuvant Paclitaxel/Olaparib in Comparison to Paclitaxel/Carboplatin in Patients with HER2-Negative Breast Cancer and HRD-Long-term Survival of the GeparOLA Study

Fasching P, Schmatloch S, Hauke J, Rey J, Jackisch C, Klare P, Link T, Hanusch C, Huober J, Stefek A, Holtschmidt J, Schneeweiss A, Uleer C, Schmitt WD, Doering G, Rhiem K, Denkert C, Schmutzler RK, Solbach C, Hahnen E, Hartkopf A, Untch M, Bjelic-Radisic V, Nekljudova V, Blohmer JU, Loibl S (2025)

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Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 31

Pages Range: 1596-1604

Journal Issue: 9

DOI: 10.1158/1078-0432.CCR-24-2806

Abstract

PURPOSE: The GeparOLA study evaluated paclitaxel plus olaparib (PO) in neoadjuvant chemotherapy for patients with HER2-negative early breast cancer with homologous recombination deficiency (HRD). HRD was defined by high HRD score or germline (g)/tumor (t) BRCA1/2 mutations (g/tBRCA1/2mut). In this study, we report long-term outcome data. PATIENTS AND METHODS: GeparOLA (NCT02789332) was a randomized, multicenter, prospective, open-label, phase II trial. Patients with HER2-negative early breast cancer with HRD with an indication for chemotherapy (cT2-cT4a-d or cT1c and cN+ or cT1c and pNSLN+ or cT1c and triple-negative breast cancer, or cT1c and Ki-67 >20%) were randomly assigned to PO or paclitaxel + carboplatin (PCb), both followed by epirubicin + cyclophosphamide. Long-term efficacy endpoints were secondary endpoints and included invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival, with a planned median follow-up of >4 years. RESULTS: Between September 2016 and July 2018, 107 patients were randomized and 106 (PO N = 69 and PCb N = 37) started treatment. The median age was 47.0 years; of all patients, 35.8% had cT1 tumors, 31.4% were cN+, 86.8% had G3 tumors, 89.6% had Ki-67 >20%, and 72.6% were triple negative. After a median follow-up of 49.8 months, 18 (15 in PO and three in PCb) iDFS events and seven (six in PO and one in PCb) deaths were reported. The 4-year iDFS (76.0% PO vs. 88.5% PCb, hazard ratio = 2.86; 95% CI, 0.83-9.90; log-rank P = 0.081), DDFS (81.2% PO vs. 93.4% PCb, hazard ratio = 3.03; 95% CI, 0.67-13.67; log-rank P = 0.129), and overall survival (89.2% PO vs. 96.9% PCb, hazard ratio = 3.27; 95% CI, 0.39-27.20; log-rank P = 0.244) tended to be inferior with olaparib. Patients without g/tBRCA1/2mut benefited from Cb (seven of 30 patients had iDFS/DDFS events in PO vs. 0/16 in PCb; log-rank P = 0.037), whereas no difference for patients with g/tBRCA1/2mut was observed (hazard ratio = 1.16, log-rank P = 0.83). CONCLUSIONS: For HER2-negative early breast cancer with HRD, olaparib showed a tendency for inferior outcomes compared with Cb, particularly in patients without g/tBRCA1/2mut. In patients with g/tBRCA1/2mut, olaparib may replace Cb.

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How to cite

APA:

Fasching, P., Schmatloch, S., Hauke, J., Rey, J., Jackisch, C., Klare, P.,... Loibl, S. (2025). Neoadjuvant Paclitaxel/Olaparib in Comparison to Paclitaxel/Carboplatin in Patients with HER2-Negative Breast Cancer and HRD-Long-term Survival of the GeparOLA Study. Clinical Cancer Research, 31(9), 1596-1604. https://doi.org/10.1158/1078-0432.CCR-24-2806

MLA:

Fasching, Peter, et al. "Neoadjuvant Paclitaxel/Olaparib in Comparison to Paclitaxel/Carboplatin in Patients with HER2-Negative Breast Cancer and HRD-Long-term Survival of the GeparOLA Study." Clinical Cancer Research 31.9 (2025): 1596-1604.

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