Breast cancer, early stage

4593 - Long-term survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative (TNBC) and HER2-positive early breast cancer (GeparSixto)

Date

09 Sep 2017

Session

Breast cancer, early stage

Presenters

Michael Untch

Citation

Annals of Oncology (2017) 28 (suppl_5): v43-v67. 10.1093/annonc/mdx362

Authors

M. Untch¹, A. Schneeweiss², C. Salat³, M. Rezai⁴, D. Zahm⁵, P. Klare⁶, J. Blohmer⁷, H. Tesch⁸, F. Khandan⁹, P.A. Fasching¹⁰, C. Jackisch¹¹, V. Nekljudova¹², G. von Minckwitz¹², S. Loibl¹²

Author affiliations

¹ Frauenklinik, Helios Klinikum Berlin Buch, 13125 - Berlin/DE
² Division Gynecologic Oncology, National Center for Tumor Diseases (NTC) University Hospital, Heidelberg/DE
³ Innere Medizin, Hämatologie Und Internistische Onkologie, Hämato-Onkologische Schwerpunktpraxis, 80639 - München/DE
⁴ Frauenklinik, Luisenkrankenhaus, Düsseldorf/DE
⁵ Frauenklinik, SRH Wald-Klinikum, Gera/DE
⁶ Krebsheilkunde, Praxisklinik, Berlin/DE
⁷ Klinik Für Gynäkologie Mit Brustzentrum, Charité-Universitätsmedizin Berlin, 10117 - Berlin/DE
⁸ Onkologie, Dr. Hans Tesch - Private Address, 60389 - Frankfurt am Main/DE
⁹ Frauenklinik, St. Markus Krankenhaus, Frankfurt/DE
¹⁰ Frauenklinik, Universitätsklinik Erlangen, 91054 - Erlangen/DE
¹¹ Frauenklinik, Klinikum Offenbach GmbH, 63069 - Offenbach/DE
¹² Medicine And Research, German Breast Group (GBG) Forschungs GmbH, 63263 - Neu-Isenburg/DE

Resources

Abstract 4593

Background

Patients (pts) with TNBC involved in the GeparSixto study showed an improved pCR rate (ypT0 ypN0) with the addition of carboplatin (Cb) to anthracycline/taxane-based neoadjuvant chemotherapy, which translated in an improved early disease-free survival (DFS). No difference was observed in the HER2+ subgroup for pCR and DFS by adding Cb. Here, we present the results on the long-term survival analysis.

Methods

In the GeparSixto trial, pts were treated for 18 weeks with paclitaxel 80mg/m² q1w and non-pegylated-liposomal doxorubicin (NPLD) 20mg/m² q1w (PM), concurrently with bevacizumab 15mg/kg q3w if TNBC or trastuzumab 6(8)mg/kg q3w and lapatinib 750mg daily if HER2+. 595 pts were randomised 1:1 to receive concurrently Cb AUC 1.5-2.0 q1w (reduced to 1.5 by an amendment after 330 pts) vs no Cb, stratified by subtype (HER+ vs TNBC), 588 pts started treatment. Primary objective was pCR (ypT0 ypN0). DFS, distant (DDFS), loco regional recurrence-free (LRRFS) and overall survival (OS) were secondary objectives.

Results

After a median follow-up of 47.3 months (range 1.7-62.8) overall no significant difference in DFS was seen with PMCb vs PM (HR = 0.83 [95%CI 0.58-1.20]; p = 0.327). However, Pts with TNBC had a significantly better DFS (HR = 0.56 [95%CI 0.34-0.93]; p = 0.024) and DDFS (HR = 0.50 [95%CI 0.29-0.86]; p = 0.013) when treated with PMCb. No difference was seen in pts with HER2+ disease (DFS HR = 1.34 [95%CI 0.77-2.34]; p = 0.295; interaction test p = 0.022 and DDFS HR = 1.56 [95% CI 0.86-2.83]; p = 0.145; interaction test p = 0.006). A trend towards a better OS was observed in pts with TNBC (HR = 0.60 [95%CI 0.32-1.12]; p = 0.110). OS was not different between the two arms, neither overall (HR = 0.72 [95%CI 0.43-1.21]; p = 0.223) nor in HER2+ disease (HR = 1.13 [95%CI 0.44-2.93]; p = 0.800). Multivariable analysis comfirms that pCR (pCR vs no pCR) independently predicted DFS (HR = 0.23, p

Conclusions

Long-term survival analysis supports the neoadjuvant use of Cb in TNBC. The value of pCR as a strong predictor of DFS and OS was confirmed.

Clinical trial identification

NCT 01426880

Legal entity responsible for the study

German Breast Group

Funding

Teva, GSK, Roche, Hexal

Disclosure

G. von Minckwitz, S. Loibl: Research grant to the institution from Teva. All other authors have declared no conflicts of interest.