A Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)

Summary

Two regimen are currently considered to have highest efficacy for patients with high-risk early stage breast cancer: sequential treatment of high dose epirubicin, taxane, and cyclophosphamide concomitantly with a dual HER2-blockade, and weekly treatment with paclitaxel/non-pegylated liposomal doxorubicin with dual HER2-blockade or carboplatin. The aim of the GeparOcto study is to compare those two regimen/strategies. Both regimens are myelosuppressive with a significant incidence of chemotherapy induced anaemia. The second aim of the GeparOcto study is therefore to compare the use of parental ferric carboxymaltose versus physician's choice for the treatment of chemotherapy-induced anemia in patients with iron deficiency.

Timeline

Start

2014-12

Primary completion

2016-11

Completion

2017-01-30

Outcome

Missed primary endpoint

paper pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77-1.28, P = 0.979) PMID 30528802 ↗

paper In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. PMID 30528802 ↗

Publications

• Schneeweiss A, Michel LL, Mobus V, Tesch H, Klare P, Hahnen E, Denkert C, Kast K, Pohl-Rescigno E, Hanusch C, Link T, Untch M, Jackisch C, Blohmer JU, Fasching PA, Solbach C, Schmutzler RK, Huober J, Rhiem K, Nekljudova V, Lubbe K, Loibl S; GBG and AGO-B. Survival analysis of the randomised phase III GeparOcto trial comparing neoadjuvant chemotherapy of intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for patients with high-risk early breast cancer. Eur J Cancer. 2022 Jan;160:100-111. doi: 10.1016/j.ejca.2021.10.011. Epub 2021 Nov 17.
• Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M, Wimberger P, Forberger A, Tesch H, Jackisch C, Schmatloch S, Reinisch M, Solomayer EF, Schmitt WD, Hanusch C, Fasching PA, Lubbe K, Solbach C, Huober J, Rhiem K, Marme F, Reimer T, Schmidt M, Sinn BV, Janni W, Stickeler E, Michel L, Stotzer O, Hahnen E, Furlanetto J, Seiler S, Nekljudova V, Untch M, Loibl S. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021 Aug;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6. Epub 2021 Jul 9.
• Ruger AM, Schneeweiss A, Seiler S, Tesch H, van Mackelenbergh M, Marme F, Lubbe K, Sinn B, Karn T, Stickeler E, Muller V, Schem C, Denkert C, Fasching PA, Nekljudova V, Garfias-Macedo T, Hasenfuss G, Haverkamp W, Loibl S, von Haehling S. Cardiotoxicity and Cardiovascular Biomarkers in Patients With Breast Cancer: Data From the GeparOcto-GBG 84 Trial. J Am Heart Assoc. 2020 Dec;9(23):e018143. doi: 10.1161/JAHA.120.018143. Epub 2020 Nov 16.
• Pohl-Rescigno E, Hauke J, Loibl S, Mobus V, Denkert C, Fasching PA, Kayali M, Ernst C, Weber-Lassalle N, Hanusch C, Tesch H, Muller V, Altmuller J, Thiele H, Untch M, Lubbe K, Nurnberg P, Rhiem K, Furlanetto J, Lederer B, Jackisch C, Nekljudova V, Schmutzler RK, Schneeweiss A, Hahnen E. Association of Germline Variant Status With Therapy Response in High-risk Early-Stage Breast Cancer: A Secondary Analysis of the GeparOcto Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):744-748. doi: 10.1001/jamaoncol.2020.0007.
• Schneeweiss A, Mobus V, Tesch H, Hanusch C, Denkert C, Lubbe K, Huober J, Klare P, Kummel S, Untch M, Kast K, Jackisch C, Thomalla J, Ingold-Heppner B, Blohmer JU, Rezai M, Frank M, Engels K, Rhiem K, Fasching PA, Nekljudova V, von Minckwitz G, Loibl S. Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial. Eur J Cancer. 2019 Jan;106:181-192. doi: 10.1016/j.ejca.2018.10.015. Epub 2018 Dec 5.

Drugs

Indications