Assessing the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency

Summary

This is a multicenter, prospective, randomized, open-label phase II study evaluating the efficacy and safety of PO→EC as neoadjuvant treatment of operable and locally advanced breast cancer in patients with HR deficiency. Patients will be randomized to receive * paclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg (4X25mg) twice daily for 12 weeks (65 patients) or * paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) both followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) either every 3 or every 2 weeks followed by surgery. The control arm was chosen to allow direct comparison with one of the currently considered standard of care regimen.

Timeline

Start

2016-09

Primary completion

2019-02

Completion

2020-02

Outcome

Missed primary endpoint

paper GeparOLA could not exclude a pCR rate of ≤55% in the PO arm. PMID 33098995 ↗

Publications

• Background Von Minckwitz G, Timms K, Untch M, Elkin E P, Fasching P A, Schneeweiss A et al. Prediction of pathological complete response (pCR) by Homologous Recombination Deficiency (HRD) after carboplatin-containing neoadjuvant chemotherapy in patients with TNBC: Results from GeparSixto. J Clin Oncol 33, 2015 (suppl; abstr 1004)
• Background Tutt A, Ellis P, Kilburn L et al. The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer. SABCS 2014.
• Background Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. doi: 10.1200/JCO.2014.57.0572. Epub 2014 Aug 4.
• Background von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, Zahm DM, Kummel S, Eidtmann H, Klare P, Huober J, Costa S, Tesch H, Hanusch C, Hilfrich J, Khandan F, Fasching PA, Sinn BV, Engels K, Mehta K, Nekljudova V, Untch M. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014 Jun;15(7):747-56. doi: 10.1016/S1470-2045(14)70160-3. Epub 2014 Apr 30.
• Results DOI: 10.1200/JCO.2019.37.15_suppl.506 Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 506-506. Fasching PA, Jackisch J, Rhiem K et al. 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). J Clin Oncol 2019; 37.15_suppl.506; oral presentation
• Fasching PA, Link T, Hauke J, Seither F, Jackisch C, Klare P, Schmatloch S, Hanusch C, Huober J, Stefek A, Seiler S, Schmitt WD, Uleer C, Doering G, Rhiem K, Schneeweiss A, Engels K, Denkert C, Schmutzler RK, Hahnen E, Untch M, Burchardi N, Blohmer JU, Loibl S; German Breast Group and Arbeitsgemeinschaft Gynakologische Onkologie Breast. Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study). Ann Oncol. 2021 Jan;32(1):49-57. doi: 10.1016/j.annonc.2020.10.471. Epub 2020 Oct 21.

Drugs

Indications