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Journal of Clinical Oncology, Vol 21, Issue 15 (August), 2003: 2889-2895
© 2003 American Society for Clinical Oncology

Trastuzumab and Vinorelbine as First-Line Therapy for HER2-Overexpressing Metastatic Breast Cancer: Multicenter Phase II Trial With Clinical Outcomes, Analysis of Serum Tumor Markers as Predictive Factors, and Cardiac Surveillance Algorithm

Harold J. Burstein, Lyndsay N. Harris, P. Kelly Marcom, Rosemary Lambert-Falls, Kathleen Havlin, Beth Overmoyer, Robert J. Friedlander, Jr., Janet Gargiulo, Rochelle Strenger, Charles L. Vogel, Paula D. Ryan, Mathew J. Ellis, Raquel A. Nunes, Craig A. Bunnell, Susana M. Campos, Michele Hallor, Rebecca Gelman, Eric P. Winer

From the Dana-Farber Cancer Institute, Brigham & Women’s Hospital, Harvard Medical School; Massachusetts General Hospital, Boston, MA; Duke University Medical Center, Durham, NC; South Carolina Oncology Associates, West Columbia, SC; Evanston Hospital, Evanston, IL; University Hospitals of Cleveland, Cleveland, OH; New Hampshire Oncology-Hematology, PA, Hooksett, NH; Capital District Hematology/Oncology, Latham, NY; Miriam and Rhode Island Hospitals, Providence, RI; Cancer Research Network, Plantation, FL.

Address reprint requests to Harold J. Burstein, MD, PhD, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115; email: hburstein{at}partners.org.

Purpose: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools.

Patients and Methods: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction >= 50%. Serial testing for HER2 extracellular domain (ECD) was performed.

Results: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression.

Conclusion: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.

Supported in part by research grants-in-aid from GlaxoSmithKlein and Genentech. Reagent test kits were supplied by Oncogene Science.


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