Trastuzumab: hopes and realities

Abstract

Despite improvements in care of patients with breast cancer, up to half develop refractory or resistant disease. There is therefore a need for new, modified anticancer therapies with greater effectiveness, tolerability to patients, and tumour specificity. Trastuzumab (Herceptin) is the first clinically available oncogene-targeted therapeutic agent for treatment of solid tumours. Clinical trials in patients positive for HER2 (human epidermal-growth-factor receptor 2) show that trastuzumab is effective and well tolerated; as a single-agent second-line or third-line treatment, the drug produced durable tumour responses. First-line trastuzumab in combination with chemotherapy, particularly paclitaxel, significantly improved time to disease progression, duration of response, and time to treatment failure. Combination therapy resulted in a 25% improvement in overall survival compared with chemotherapy alone. Patients with HER2 gene amplification, high overexpression of HER2 (3+ on immunohisto-chemistry), or both features, obtained the greatest clinical benefit. Trastuzumab is the first monoclonal antibody with efficacy in breast cancer and the first gene-product-targeted therapy to produce a significant survival advantage in this disease. Trastuzumab is likely to find its ultimate role in the adjuvant setting. Its development provides a model for the integration of other gene-targeted therapies into breast-cancer management to improve survival and quality of life.