Efficacy and safety of nab-paclitaxel 125 mg/m2 and nab-paclitaxel 150 mg/m2 compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69)
- 1.2k Downloads
The GeparSepto study demonstrated that the use of nab-paclitaxel instead of paclitaxel prior to anthracycline-based chemotherapy could lead to a significantly increased pCR rate, especially in the triple negative subpopulation. We report efficacy and safety for patients treated with two different doses of nab-paclitaxel in comparison to weekly solvent-formulated paclitaxel.
Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m2 (nP150) weekly, after study amendment 125 mg/m2 (nP125) weekly or solvent-based paclitaxel 80 mg/m2 (P80) weekly followed by epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 on day 1 for four 3-week cycles.
229 patients received nP150, 377 nP125. Baseline characteristics were fairly balanced between these two sequential cohorts as well as compared to 601 patients receiving P80 except for hormone receptor status, HER2 status, and Ki67. Taxane treatment was discontinued in 26.8% (nP150), 16.6% (nP125), and 13.3% of (P80) patients, respectively. Median relative total dose intensity (mRTDI) based on 125 mg/m2 for nP was 103% with nP150, 95% with nP125, 99% with P80 before and 98% with P80 after the amendment. PSN grade 3–4 was observed in 14.5% of patients with nP150, 8.1% of patients with nP125 (p = 0.018), and 2.7% of patients with P80. Overall pCR before the amendment was 33.6% after nP150 and 23.5% after P80 (OR 1.65 [95% CI 1.10–2.50]; p = 0.022); pCR after the amendment was 41.4% after nP125, and 32.4% after P80 (1.48 [95% CI 1.10–1.99]; p = 0.013).
Nab-paclitaxel 125 mg/m2 was associated with a better safety profile and compliance without compromising the efficacy compared to nab-paclitaxel 150 mg/m2.
KeywordsEarly breast cancer Neoadjuvant treatment Nab-paclitaxel 125 mg/m2 Nab-paclitaxel 150 mg/m2
We would like to thank all investigators and patients that participated in the GeparSepto study.
The trial was sponsored by GBG Forschungs GmbH with financial support from Celgene and Roche.
Compliance with ethical standards
Conflict of interest
Denkert C: Shareholder and cofounder of Sividon Diasgnostics Cologne, Hanusch C: Honoraria by Celgene and Roche, Jakisch C: Honoraria by Celgene, Loibl S: Institution received research grants by Celgene and Roche, von Minckwitz G: Institution received research grants by Celgene and Roche. All other authors have declared no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the GeparSepto study.
- 2.Gianni L, Baselga J, Eiermann W et al (2009) Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol 27:2474–2481CrossRefPubMedGoogle Scholar
- 20.Peng L, Bu Z, Ye X et al (2015) Incidence and risk of peripheral neuropathy with nab-paclitaxel in patients with cancer: a meta-analysis. Eur J Cancer Care (in press)Google Scholar
- 21.Gianni L, Mansutti M, Anton A et al (2016) ETNA (Evaluating Treatment with Neoadjuvant Abraxane) randomized phase III study comparing neoadjuvant nab-paclitaxel (nab-P) versus paclitaxel (P) both followed by anthracycline regimens in women with HER2-negative high-risk breast cancer: a MICHELANGO study. J Clin Oncol 34 (suppl; abstr 502)Google Scholar
- 22.Kümmel S, von Minckwitz G, Nekljudova V et al (2016) Investigating denosumab as add-on neoadjuvant treatment for hormone receptor-negative, RANK-positive or RANK-negative primary breast cancer and two different nab-Paclitaxel schedules – 2 × 2 factorial design (GeparX). J Clin Oncol 34 (suppl; abstr TPS635)Google Scholar
- 23.Huang L, Chen S, Yao L et al (2015) Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer. Int J Nanomed 10:1969–1975Google Scholar
- 24.Sinclair NF, Abu-Khalaf MM, Rizack T et al (2012) Neoadjuvant weekly nab-paclitaxel, carboplatin plus bevacizumab with or without dose-dense doxorubicin-cyclophosphamide (ddAC) plus bevacizumab in ER+/HER2-negative (HR+) and triple-negative breast cancer: a BrUOG study. J Clin Oncol 30 (suppl, abstr 1045)Google Scholar
- 25.Mrozek E, Lustberg MB, Knopp MV et al (2010) Phase II trial of neoadjuvant chemotherapy with weekly nanoparticle albumin-bound paclitaxel, carboplatin, and bevacizumab in women with clinical stages II-III breast cancer: pathologic response prediction by changes in angiogenic volume by dynamic contrast magnetic resonance imaging (DCE-MRI). J Clin Oncol 28 (suppl, abstr 604)Google Scholar
- 27.Carboplatin and paclitaxel albumin-stabilized nanoparticle formulation before surgery in treating patients with locally advanced or inflammatory triple negative breast cancer (2015) ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01525966