Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens.
OBJECTIVE
Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast cancer (MBC). Preclinical findings of synergy between docetaxel, carboplatin, and trastuzumab (TCH) prompted a phase III randomized trial comparing TCH with TH in patients with HER2-amplified MBC.


METHODS
Two hundred sixty-three patients were randomly assigned to receive eight 3-week cycles of TH (trastuzumab plus docetaxel 100 mg/m(2)) or TCH (trastuzumab plus carboplatin at area under the serum concentration-time curve 6 and docetaxel 75 mg/m(2)). Trastuzumab was given at 4 mg/kg loading dose followed by a 2 mg/kg dose once per week during chemotherapy, and then 6 mg/kg once every 3 weeks until progression.


RESULTS
Patient characteristics were balanced between groups. There was no significant difference between TH and TCH in terms of the primary end point, time to progression (medians of 11.1 and 10.4 months, respectively; hazard ratio, 0.914; 95% CI, 0.694 to 1.203; P = .57), response rate (72% for both groups), or overall survival (medians of 37.1 and 37.4 months, respectively; P = .99). Rates of grades 3 or 4 adverse effects for TH and TCH, respectively, were neutropenic-related complications, 29% and 23%; thrombocytopenia, 2% and 15%; anemia, 5% and 11%; sensory neuropathy, 3% and 0.8%; fatigue, 5% and 12%; peripheral edema, 3.8% and 1.5%; and diarrhea, 2% and 10%. Two patients given TCH died of sepsis, and one patient given TH experienced sudden cardiac death. Absolute left ventricular ejection fraction decline > 15% was seen in 5.5% of patients on the TH arm and 6.7% of patients on the TCH arm.


CONCLUSIONS
Adding carboplatin did not enhance TH antitumor activity.TH (docetaxel, 100 mg/m(2)) and TCH (docetaxel, 75 mg/m(2)) demonstrated efficacy with acceptable toxicity in women with HER2-amplified MBC.
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. vvalero@mdanderson.org
Vicente
V
Valero
John
J
Forbes
Mark D
MD
Pegram
Tadeusz
T
Pienkowski
Wolfgang
W
Eiermann
Gunter
G
von Minckwitz
Henri
H
Roche
Miguel
M
Martin
John
J
Crown
John R
JR
Mackey
Pierre
P
Fumoleau
Janusz
J
Rolski
Zrinka
Z
Mrsic-Krmpotic
Agnieszka
A
Jagiello-Gruszfeld
Alessandro
A
Riva
Marc
M
Buyse
Henry
H
Taupin
Guido
G
Sauter
Michael F
MF
Press
Dennis J
DJ
Slamon
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* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human