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Breast cancer, metastatic

4430 - A phase II trial of Dasatinib (D) in combination with trastuzumab (T) and paclitaxel (P) in the first line treatment of HER2 positive Metastatic Breast Cancer (MBC) patients (pts): GEICAM/2010-04


10 Sep 2017


Breast cancer, metastatic


Cytotoxic Therapy;  Breast Cancer


Alberto Ocana Fernandez


Annals of Oncology (2017) 28 (suppl_5): v74-v108. 10.1093/annonc/mdx365


A. Ocana Fernandez1, M. Ruíz-Borrego2, M. Gil Martin3, S. Antolin4, M. Atienza2, A. Montaño2, N. Ribelles5, A. Guerrero6, M. Muñoz7, I. Fernández-Pérez8, A. Urruticoechea9, A. Falcon Gonzalez10, S. Pernas Simon11, J. Prato Varela12, M.J. Escudero13, S. Benito14, R. Caballero15, E. Carrasco16, F. Rojo17, A. Pandiella18

Author affiliations

  • 1 Clinical Oncology, Complejo Hospitalario Universitario de Albacete, 2006 - Albacete/ES
  • 2 Medical Oncology, Hospital Virgen del Rocío, Sevilla/ES
  • 3 Medical Oncology, Institut Català d'Oncologia (ICO)-Hospitalet, Barcelona/ES
  • 4 Clinical Oncology, Complejo Hospitalario U A Coruña, Coruña/ES
  • 5 Medical Oncology, Hospital Clínico Universitario Virgen de la Victoria, Malaga/ES
  • 6 Medical Oncology, Instituto Valenciano de Oncología, Valencia/ES
  • 7 Clinical Oncology, H Clinic i Provincial de Barcelona, Barcelona/ES
  • 8 Medical Oncology, Hospital Alvaro Cunqueiro, Vigo/ES
  • 9 Clinical Oncology, Fundación Onkologikoa, Donosti/ES
  • 10 Medical Oncology, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 11 Medical Oncology, Institut Català d'Oncologia (ICO)-Hospitalet, 08908 - Barcelona/ES
  • 12 Medical Oncology, Complejo Hospitalario Universitario A Coruña, 15006 - A Coruna/ES
  • 13 Statistics, GEICAM, 28703 - San Sebastian de los Reyes/ES
  • 14 Operations, GEICAM, 28703 - San Sebastian de los Reyes/ES
  • 15 Traslational Research Director, GEICAM, 28703 - San Sebastian de los Reyes/ES
  • 16 Scientific Director, GEICAM, Madrid/ES
  • 17 Cancer Institute, Hospital Universitario Fundación Jimenez Diaz, GEICAM, CIBERONC-ISCIII, 28040 - Madrid/ES
  • 18 Oncology, Centro de Investigación del Cáncer and CIBERONC, CSIC-Universidad de Salamanca, Salamanca/ES


Abstract 4430


In HER2 overexpressing MBC around 40% of pts treated with T-based regimens do not respond and half of them progress within a year. The combination of the SRC inhibitor D and T is synergistic in preclinical models. We conducted a phase II trial combining D with a standard first line treatment with T/P.


Pts with HER2+ MBC (by central laboratory) were included. First line treatment consisted of 28-day cycles with T 2mg/kg weekly, P 80mg/m2 (3 weeks on/1 week off) and D 100mg once daily administered in first line until radiologic or symptomatic progression (PD) or unacceptable toxicity. Primary objective was objective response rate (ORR); secondary objectives were safety, other efficacy variables (Clinical Benefit Rate (CBR), Time to Progression (TTP), Progression Free Survival (PFS)) and pharmacodynamic biomarkers (phosphorylated (p)-AKT, and p-SRC) in peripheral mononuclear cells (PBMCs).


Twenty-nine pts were included; median age was 49 years (31-81), 12 pts (41%) were premenopausal, 22 (76%) had hormone-receptor positive tumors and 23 (79.3%) had visceral disease. The median number of cycles was 12 (1-35), 9 pts discontinued treatment due to PD, 6 for adverse events, 6 due to investigator/sponsor criteria and 8 due to other reason. The ORR was 79.3% (95% CI 60.3-92) and the CBR was 82.8% (95% CI 64.2-94.2). Median TTP was 23.9 months (95% CI 14.9-not reached (NR)) and median PFS was 23.9 months (95% CI 10.3-NR). The mean relative dose intensity of D, T and P was 98.3%, 99.8% and 89.7% respectively. G2-3 decrease in ejection fraction was seen in 10.3% (n = 3) and 24.1% (n = 7) of pts. No G4 toxicity was seen. G3 toxicities were limited to: fatigue, hypertension, neutropenia and hyponatremia (6.9% [n = 2] each). Phosphorylated SRC and AKT were reduced in PBMCs after 8h (4.4 and 1.9 folds, respectively) of D administration in cycle 1 day 1 in 16 assessed pts.


D can be safely combined with T and P and the combination is effective with a ORR that reached almost 80% of patients. We observed decreased levels of p-SRC and p-AKT in PBMCs in patients treated with D, as previously described in preclinical models.

Clinical trial identification


Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group


Bristol-Myers Squibb (BMS)


All authors have declared no conflicts of interest.

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