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.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Marty
Michel
M
Institut Gustave-Roussy, Villejuif, France. memarty@free.fr
Cognetti
Francesco
F
Maraninchi
Dominique
D
Snyder
Ray
R
Mauriac
Louis
L
Tubiana-Hulin
Michèle
M
Chan
Stephen
S
Grimes
David
D
Antón
Antonio
A
Lluch
Ana
A
Kennedy
John
J
O'Byrne
Kenneth
K
Conte
PierFranco
P
Green
Michael
M
Ward
Carol
C
Mayne
Karen
K
Extra
Jean-Marc
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000077143:Docetaxel; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab