255O - Dual blockade with afatinib and trastuzumab as neoadjuvant treatment for patients with locally advanced or operable breast cancer receiving taxane-...

Date 29 September 2014
Event ESMO 2014
Session Breast cancer, early stage
Topics Anticancer Agents
Breast Cancer
Biological Therapy
Presenter Claus Hanusch
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors C.A. Hanusch1, A. Schneeweiss2, M. Untch3, S. Paepke4, S. Kümmel5, C. Jackisch6, J. Huober7, J. Hilfrich8, B. Gerber9, H. Eidtmann10, C. Denkert11, S. Costa12, J.U. Blohmer13, S. Loibl14, N. Burchardi14, G. von Minckwitz14
  • 1Frauenklinik, Rotkreuzklinikum München, 80637 - München/DE
  • 2University Hospital, National Center for Tumor Diseases, Heidelberg/DE
  • 3Frauenklinik, HELIOS Klinikum Berlin-Buch, Berlin/DE
  • 4Frauenklinik, Uniklinik München, München/DE
  • 5Klinik Für Senologie / Brustzentrum, Kliniken Essen Mitte, Essen/DE
  • 6Oncology, Klinikum Offenbach GmbH, Offenbach/DE
  • 7Frauenklinik, Universitätsklinik Ulm, Ulm/DE
  • 8Frauenklinik, Eilenriedeklinik.de, Hannover/DE
  • 9Frauenklinik, Uniklinik Rostock, Rostock/DE
  • 10Klinik Für Gynäkologie Und Geburtshilfe, Universitäts Frauenklinik Kiel, Kiel/DE
  • 11Institute Of Pathology, Charité, Campus Virchow Klinikum, 10117 - Berlin/DE
  • 12Universitäts-frauenklinik, Otto-von-Guericke-Universität, Magdeburg/DE
  • 13Frauenklinik, Sankt Gertrauden-Krankenhaus GmbH, Berlin/DE
  • 14Medicine And Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg/DE



Neoadjuvant chemotherapy uses anthracycline/taxane based combinations of ≥18 weeks as standard treatment. Concurrent administration of trastuzumab in HER2+ disease achieves a pCR rate (ypT0 ypN0) of approx. 40%. Dual anti-HER2 blockade can increase the rate by another 20%. DAFNE (NCT015591477) investigates the combination of afatinib (BIBW 2992), an irreversible ErbB-family blocker with trastuzumab.


DAFNE is a multicenter, prospective, open-label phase II study evaluating efficacy and safety of afatinib in combination with weekly paclitaxel + trastuzumab followed by epirubicin/cyclophosphamide/trastuzumab (ECH) as neoadjuvant therapy in untreated, centrally HER2 + , operable or locally advanced breast cancer patients. All patients were treated for 30 weeks: 6 weeks with afatinib (20mg) and trastuzumab (8/6mg/kg); 12 weeks with additional weekly paclitaxel (80mg/m2); and 12 weeks with ECH according to standard. Afatinib was given every other day for the first 2 weeks to reduce the risk of diarrhea and skin toxicities. Primary prophylaxis with loperamide 2x2mg daily was mandatory for the first 4 weeks of afatinib/trastuzumab and the first 2 weeks of paclitaxel. Primary objective is pCR rate (ypT0/is ypN0). Assuming a pCR rate of 70% with α = 0.1 and 80% power, a pCR of ≤55% should be excluded. Secondary objectives are pCR by other definitions, clinical response rates, rate and type of surgery, toxicity, compliance, pCR related to skin toxicity and diarrhea and pre-specified molecular markers.


65 patients were recruited (5/2012 - 7/2013) in 11 German centers. Median age was 50 years. 9.4% had T3/4, 48.5% N + , 89.2% ductal invasive, 60% G3 and 70.8% HR+ tumors. Of the 22 SAEs (in 16 patients), 27.3% were gastrointestinal, 18.2% hematologic, 13.6% infections and 9.1% related to the nervous system. pCR rate was 49.2% (90% CI: 38.5; 60.1).


Despite a tolerable safety profile of the dual blockade with afatinib, the pCR rate was lower than expected. A subsequent phase 3 study cannot be supported. Boehringer Ingelheim, Germany supported this trial.


G. von Minckwitz: Research Grants: Boehringer-Ingelheim. All other authors have declared no conflicts of interest.