ISTANBUL, Turkey—A multinational phase II study, known as CHAT, has shown that a three-drug combination including docetaxel(Drug information on docetaxel) (Taxotere), trastuzumab(Drug information on trastuzumab) (Herceptin), and capecitabine(Drug information on capecitabine) (Xeloda) provides significantly longer time to progression (TTP) and a trend toward longer progression-free survival, compared with docetaxel plus trastuzumab, in patients with HER2-positive metastatic breast cancer. Andrew Wardley, MD, of Christie Hospital, Manchester, United Kingdom, presented the study results at the 31st Congress of the European Society for Medical Oncology (ESMO) (Late Breaking Abstract 6).
In the study, 110 patients received trastuzumab, 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks, and docetaxel 100 mg/m2 every 3 weeks, while 112 received the same trastuzumab dose, a lower docetaxel dose (75 mg/m2), plus capecitabine 940 mg/m2 twice daily on days 1 to 14 every 3 weeks. “We started at a lower dose of capecitabine than in some other studies,” Dr. Wardley said. Patients in the two-drug arm with disease progression were given the option to cross over to receive capecitabine. The primary endpoint of the study was overall response rate (ORR), which includes complete response, partial response, and stable disease.
During a median follow-up of about 18 months, the researchers saw an overall response rate of 71% in the tripledrug arm, compared with 73% in the two-drug arm, a nonsignificant difference. “The ORRs in both arms are excellent,” Dr. Wardley commented. “It really shows that trastuzumab and docetaxel and also these drugs with capecitabine are good combinations for this patient group.”
The percentage of patients achieving a complete response was 18% in the three-drug combination arm and 15% in the two-drug arm. “That’s also very good,” Dr. Wardley said. “That might be something worth looking at in patients with earlier stages of breast cancer because you may be able to eliminate disease in some patients.”
Median time to progression (time from randomization until tumor growth) showed a significant benefit of adding capecitabine to the two-drug regimen. In the three-drug arm, time to progression was 18.2 months, compared with 13.8 months in the two-drug arm (P = .045). “The improvement in time to progression with capecitabine is interesting,” Dr. Wardley said. “It’s about 4.5 months, which in other studies has been shown to be an important result.”
There was also a trend toward an increase in progression-free survival (time from randomization to tumor growth or death) with the three-drug combination, from a median of 12.8 months to 14.8 months (P = .06).
No unexpected safety concerns were noted by the external Data Safety Monitoring Board, and the incidence of cardiac failure was low (one patient in each treatment arm), Dr. Wardley said.