Trastuzumab: hopes and realities.
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.
Leyland-Jones
Brian
B
Department of Oncology, McGill University, Montreal, Quebec Canada. leylandj@med.mcgill.ca
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000187:drug effects*; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab