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Trastuzumab/Vinorelbine Safe, Effective First-line Treatment for Advanced Breast Cancer

Combinatorial trastuzumab/vinorelbine therapy is a safe, well-tolerated and effective initial treatment for women with HER2-postive metastatic breast cancer, according to a recent American phase II study.

Trastuzumab-based chemotherapy has become a standard treatment for women with HER2-positive advanced breast cancer. However, the optimal regimen and the therapy duration have yet to be characterised.

Concurrent trastuzumab and vinorelbine treatment previously showed synergistic effects in laboratory studies and a recent single centre study revealed favourable response with this combinatorial treatment.

Harold J. Burstein, MD, PhD, at the Dana-Farber Cancer Institute, Boston, Massachusetts, United States, and colleagues throughout the US conducted a multi-centre study to evaluate trastuzumab/vinorelbine as a combinatorial first-line therapy for women with HER2-positive advanced breast cancer.

This study included 54 women (ages 29 to 82) with HER2-positive stage IV breast cancer that received trastuzumab (initial 4 mg/kg, weekly 2 mg/kg) and vinorelbine (weekly maximum dose 25 mg/m²). Tumour response was evaluated after every 8 week cycle. Cardiotoxicity was monitored by left ventricular ejection fraction (LVEF) screening at 16 weeks.

A positive response to treatment was observed in 68% (37) of patients, with 4 patients showing complete response. Furthermore, 9 patients had stable disease for 6 months or longer.

Overall, the average time to treatment failure was 5.6 months and 38% of patients were progression-free after 1 year. Thirty-one patients discontinued treatment due to eventual tumour progression and 5 patients due to excessive toxicity.

Overall, acute and chronic adverse events were tolerable. The most common events were neutropenia (72% of patients) and fatigue (80% of patients).

Cardiotoxicity was observed in 2 patients, one of which experienced symptomatic heart failure. LVEF successfully identified these women to be at risk for cardiotoxicity.

Neither baseline levels nor decreases in HER2 could predict clinical response. However, lack of decline during the first 8 weeks of treatment could predict tumour progression.

Dr. Burstein concludes that the "data support the use of trastuzumab and vinorelbine as a safe, well-tolerated, and effective first-line treatment for women with HER2-positive metastatic breast cancer." Furthermore, LVEF at 16 weeks can be used "to identify those at risk for cardiotoxicity."

The authors are supported in part by research grants-in-aid from GlaxoSmithKlein and Genentech.
J Clin Oncol 2003 Aug 1;21:15:2889-95. "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"

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