A multinationalphase II study, known as CHAT,has shown that a three-drug combinationincluding docetaxel (Taxotere),trastuzumab (Herceptin), and capecitabine(Xeloda) provides significantlylonger time to progression (TTP) and atrend toward longer progression-free survival,compared with docetaxel plustrastuzumab, in patients with HER2-positivemetastatic breast cancer.
ISTANBUL, Turkey--A multinationalphase II study, known as CHAT,has shown that a three-drug combinationincluding docetaxel (Taxotere),trastuzumab (Herceptin), and capecitabine(Xeloda) provides significantlylonger time to progression (TTP) and atrend toward longer progression-free survival,compared with docetaxel plustrastuzumab, in patients with HER2-positivemetastatic breast cancer. Andrew Wardley, MD, of Christie Hospital,Manchester, United Kingdom,presented the study results atthe 31st Congress of the EuropeanSociety for MedicalOncology (ESMO) (LateBreaking Abstract 6).
In the study, 110 patientsreceived trastuzumab, 8 mg/kgloading dose followed by 6 mg/kgevery 3 weeks, and docetaxel 100mg/m2 every 3 weeks, while 112 receivedthe same trastuzumab dose, alower docetaxel dose (75mg/m2), plus capecitabine 940mg/m2 twice daily on days 1to 14 every 3 weeks. "Westarted at a lower dose ofcapecitabine than in someother studies," Dr. Wardley said.Patients in the two-drug armwith disease progression were given the option to cross over to receive capecitabine.The primary endpoint of thestudy was overall response rate (ORR),which includes complete response, partialresponse, and stable disease.
During a median follow-up of about18 months, the researchers saw an overallresponse rate of 71% in the tripledrugarm, compared with 73% in thetwo-drug arm, a nonsignificant difference."The ORRs in both arms are excellent,"Dr. Wardley commented. "Itreally shows that trastuzumab anddocetaxel and also these drugs withcapecitabine are good combinations forthis patient group."
The percentage of patients achievinga complete response was 18% in thethree-drug combination arm and 15%in the two-drug arm. "That's also verygood," Dr. Wardley said. "That mightbe something worth looking at in patientswith earlier stages of breast cancerbecause you may be able to eliminatedisease in some patients."
Median time to progression (timefrom randomization until tumor growth)showed a significant benefit of addingcapecitabine to the two-drug regimen.In the three-drug arm, time to progressionwas 18.2 months, compared with13.8 months in the two-drug arm(P = .045). "The improvement in time toprogression with capecitabine is interesting,"Dr. Wardley said. "It's about 4.5months, which in other studies has beenshown to be an important result."
There was also a trend toward an increasein progression-free survival (timefrom randomization to tumor growth ordeath) with the three-drug combination,from a median of 12.8 months to 14.8months (P = .06).
No unexpected safety concerns werenoted by the external Data Safety MonitoringBoard, and the incidence of cardiacfailure was low (one patient in eachtreatment arm), Dr. Wardley said.
At the time of the study presentation,overall survival results were immaturedue to short follow-up. Final data analysisis expected in 2007.
The researchers concluded that bothcombinations are effective first-line regimensfor patients with HER2-positivemetastatic breast cancer. "It does showthat we're potentially getting better attreating patients in this situation," Dr.Wardley said. "The encouraging thing isthat we now have some good treatmentoptions for patients with HER2-positivebreast cancer."