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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

Date

10 Sep 2017

Session

Breast cancer, metastatic

Presenters

Alberto Ocana Fernandez

Citation

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

Authors

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
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Resources

Abstract 4430

Background

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.

Methods

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).

Results

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.

Conclusions

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

NCT01306942

Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group

Funding

Bristol-Myers Squibb (BMS)

Disclosure

All authors have declared no conflicts of interest.

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