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Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer: activity and safety results from a phase II study

Thomas Bachelot1, Jose A Garcia-Saenz2, Sunil Verma3, Maya Gutierrez4, Xavier Pivot5, Mark F Kozloff6, Catherine Prady7, Xin Huang8, Reza Khosravan8, Zhixiao Wang129, Rossano Cesari10, Vanessa Tassell138, Kenneth A Kern8, Jean-Yves Blay114* and Ana Lluch11

Author Affiliations

1 EORTC, Soft Tissue and Bone Sarcoma Group, Centre Léon-Bérard and Université Claude Bernard, Lyon, France

2 Hospital Clinico San Carlos, Madrid, Spain

3 Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Canada

4 Medical Oncology, René Huguenin Cancer Centre, Saint Cloud, France

5 Hôpital Jean Minjoz, Besançon, France

6 University of Chicago, Chicago, and Ingalls Memorial Hospital, Harvey, IL, USA

7 Centre intégré de cancérologie de la Montérégie, CSSS Champlain-Charles-Lemoyne, Greenfield Park, Quebec, Canada

8 Pfizer Oncology, La Jolla, CA, USA

9 Pfizer Oncology, New York, NY, USA

10 Pfizer Oncology, Milan, Italy

11 INCLIVA-Servicio de Oncología Médica, Hospital Clínico Universitario de Valencia, Valencia, Spain

12 Previous employee of Pfizer; current affiliation: Eisai Inc., Woodcliff Lake, NJ, USA

13 Previous employee of Pfizer; current affiliation: Aragon Pharmaceuticals Inc., San Diego, CA, USA

14 Léon Bérard Comprehensive Cancer Centre, Université Claude Bernard Lyon I, 28 rue Laennec, F-69008 Lyon, France

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BMC Cancer 2014, 14:166  doi:10.1186/1471-2407-14-166

Published: 7 March 2014



This phase II study evaluated the efficacy and safety/tolerability of sunitinib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC).


Eligible patients received sunitinib 37.5 mg/day and trastuzumab administered either weekly (loading, 4 mg/kg; then weekly 2 mg/kg) or 3-weekly (loading, 8 mg/kg; then 3-weekly 6 mg/kg). Prior trastuzumab and/or lapatinib treatment were permitted. The primary endpoint was objective response rate (ORR).


Sixty patients were enrolled and evaluable for safety; 57 were evaluable for efficacy. The majority of patients (58%) had received no prior chemotherapy in the metastatic setting. The ORR was 37%; the clinical benefit rate (CBR; percent objective response plus stable disease ≥ 24 weeks) was 56%. Among patients who were treatment-naïve or had received only adjuvant therapy, the ORR was 44% and the CBR was 59%. Overall, median overall survival had not been reached and the 1-year survival rate was 91%. The majority of adverse events (AEs) were mild to moderate in severity. Forty percent of patients experienced AEs related to measured left ventricular ejection fraction (LVEF) declines, which occurred more frequently in patients who had received prior anthracycline treatment. Ten percent of patients exhibited symptoms related to LVEF declines. One patient died on study from cardiogenic shock. Antitumor response and several safety parameters appeared to correlate with sunitinib exposure.


Sunitinib plus trastuzumab demonstrated antitumor activity in patients with HER2-positive ABC, particularly those who were treatment-naïve or had only received prior adjuvant treatment. Sunitinib plus trastuzumab had acceptable safety and tolerability in patients with HER2-positive ABC who had not received prior anthracycline therapy.

Trial registration


Sunitinib; Trastuzumab; Advanced breast cancer