ATLANTA—When used as first-line therapy for metastatic HER2-positive breast cancer, docetaxel(Drug information on docetaxel) (Taxotere) plus trastuzumab(Drug information on trastuzumab) (Herceptin) (TH) has similar efficacy to docetaxel, carboplatin(Drug information on carboplatin), and trastuzumab (TCH), but the toxicity profiles differ, finds a randomized phase III trial presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (abstract 516).

"Docetaxel, carboplatin, and trastuzumab are all active agents, and there is a substantial biological basis for suggesting that carboplatin and Herceptin may be synergistic," said John F. Forbes, MD, professor of surgical oncology, University of Newcastle, Australia.

Patients eligible for the multicenter trial (BCIRG 007) had HER2-positive metastatic breast cancer and had not received any treatment for their metastatic disease. They were assigned to TH—eight cycles of docetaxel 100 mg/m2 every 3 weeks plus trastuzumab 2 mg/kg weekly after a loading dose, followed by maintenance trastuzumab 6 mg/kg every 3 weeks until progression—or TCH—eight cycles of docetaxel 75 mg/m2 every 3 weeks plus carboplatin to AUC 6 plus trastuzumab, followed by maintenance trastuzumab. The docetaxel dose was reduced in the TCH arm, Dr. Forbes said, because the lower dose was one they "believed would be readily deliverable with acceptable toxicity."

A total of 253 patients were enrolled. The median duration of follow-up was about 28 months in each group.

By intention-to-treat analysis, there was no significant difference between the TH and TCH groups in the median time to progression, the trial's primary endpoint (11.1 vs 10.4 months, respectively), Dr. Forbes said. In addition, the two groups had essentially the same rates of overall response (72.5% vs 72.7%) and median duration of response (10.7 vs 9.4 months). Median overall survival was also statistically indistinguishable, with the value not yet reached in the TH arm and 41.7 months in the TCH arm.

Toxicity Results

In terms of nonhematologic toxicities of any grade, patients in the TH group had higher incidences of sensory neuropathy (57% vs 44%), myalgia (44% vs 31%), rash/desquamation (32% vs 15%), and nail changes (55% vs 33%).

Patients in the TCH arm had higher incidences of grade 3-4 thrombocytopenia (15% vs 2%), nausea (3.8% vs 0%), and vomiting (3% vs 1.5%).