Randomized Phase II Trial of the Efficacy and Safety of Trastuzumab Combined With Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Administered As First-Line Treatment: The M77001 Study Group

• Published in: Journal of clinical oncology Vol. 23; no. 19; pp. 4265 - 4274
• Main Authors: MARTY, Michel, COGNETTI, Francesco, KENNEDY, John, O'BYRNE, Kenneth, CONTE, Pier Franco, GREEN, Michael, WARD, Carol, MAYNE, Karen, EXTRA, Jean-Marc, MARANINCHI, Dominique, SNYDER, Ray, MAURIAC, Louis, TUBIANA-HULIN, Michèle, CHAN, Stephen, GRIMES, David, ANTON, Antonio, LLUCH, Ana
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01-07-2005; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Drug Evaluation; Female; Humans; Leukopenia - chemically induced; Medical sciences; Middle Aged; Neoplasm Metastasis; Neutropenia - chemically induced; Receptor, ErbB-2 - metabolism; Taxoids - administration & dosage; Taxoids - adverse effects; Trastuzumab; Tumors; Antineoplastic agent; Human; Toxicity; Treatment efficiency; Docetaxel; Breast cancer; Monoclonal antibody; Metastasis; Malignant tumor; Human Epidermal growth factor Receptor 2; First line treatment; Mammary gland diseases; Cancerology; Taxane derivatives; Anticytokine; Phase II trial; Clinical trial; Advanced stage; Antimitotic; Trastuzumab
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.04.173

This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC).
Patients were randomly assigned to six cycles of docetaxel 100 mg/m2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression.
A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months.
Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity.