264PD - GAIN2: Adjuvant phase III trial comparing an intensified dose-dense adjuvant therapy with EnPC compared with a dose-dense, dose-adapted therapy wit...

Date 27 September 2014
Event ESMO 2014
Session Breast cancer, early stage
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Presenter Stefanie Noeding
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors S. Noeding1, H. Forstbauer2, G. Wachsmann3, A. Ober4, A. Schneeweiss5, B. Christensen6, E. von Abel7, E. Grischke8, H. Höffkes9, P. Klare10, Y. Ko11, S. Schmatloch12, N. Burchardi13, S. Loibl13, G. von Minckwitz13, V. Möbus14
  • 1Gynäkologisch-onkologische, Schwerpunktpraxis, 30177 - Hannover/DE
  • 2Brustzentrum, GOSPL - Gesellschaft für onkologische Studien, Rheinsieg/DE
  • 3Frauenklinik, Klinikum Sindelfingen-Böblingen, Böblingen/DE
  • 4Brustzentrum, St. Vincenz Krankenhaus, Limburg/DE
  • 5University Hospital, National Center for Tumor Diseases, Heidelberg/DE
  • 6Brustzentrum, Ruppiner Kliniken, Neuruppin/DE
  • 7Frauenklinik, Klinikum Schwäbisch-Gmünd, Schwäbisch-Gmünd/DE
  • 8Frauenklinik, Uniklinik Tübingen, Tübingen/DE
  • 9Frauenklinik, Klinikum Fulda, Fulda/DE
  • 10Oncologie, Praxis Berlin, Berlin/DE
  • 11Frauenklinik, Evangelische Kliniken Bonn, Bonn/DE
  • 12Frauenklinik, Elisabeth Krankenhaus, Kassel/DE
  • 13Medicine And Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg/DE
  • 14Klinik Für Gynäkologie Und Geburtshilfe, Klinikum Frankfurt Höchst GmbH, Frankfurt/DE



Combined chemotherapy requires compromises in terms of dosage and treatment interval due to toxicities. The sequential administration of monotherapies allows high doses of single substances and dose-dense intervals. So far, such regimens have proved to be very effective in early breast cancer with high risk of recurrence. Nab-paclitaxel (nP) leads to a more favorable toxicity profile and greater efficacy compared with solvent-based taxanes.


The GAIN2 study compares toxicity and efficacy of a pre-defined dose-dense high-dose regimen (EnPC) with a dose-dense regimen, where single doses are adjusted depending on individual haematological and non-haematological toxicities (dtEC-dtD). Primary endpoint is the invasive disease-free survival in patients with primary node-positive or high-risk node-negative breast cancer.

Two safety interim analyses after 200 and 900 patients who have completed chemotherapy are planned. The results of the first safety analysis will be presented. In addition to the standard analyses for haematological and non-haematological toxicities, any affections of the cranial nerves as well as the rate of macular degeneration and anaphylactic reactions are of special interest.


In terms of hematological adverse events, the rate of febrile neutropenia grade 3-4 (14% vs. 5%) and thrombocytopenia grade 3-4 (14% vs. 5%) was significantly increased in the EnPC arm. As for the non-haematological side effects, there were significantly more patients developing anorexia (grade 1-4) in the EnPC arm. There were no differences between the treatment arms for the toxicities of special interest. In the EnPC arm, 28% required dose-reductions due to hematological toxicities compared with only 11% in the dtEC dtD arm (p = 0.002). The dose could be escalated to the maximum in half of the patients receiving dtEC dtD. In 7% of women a reduction was required in the 4th cycle of docetaxel.


Due to similar toxicity profiles, the study will be continued without changes.


A. Schneeweiss: Honoraria, Research Funding and Advisory Role: Celgene and Roche; G. von Minckwitz: Honoraria and Research Funding: Amgen, Celgene and Roche; V. Möbus: Honoraria and Research Funding: Amgen, GSK, Sanofi-Aventis, Pfizer, Roche. All other authors have declared no conflicts of interest.