Efficacy
In the GeparQuinto trial, 307 patients with HER-2 positive operable or locally advanced breast cancer received neoadjuvant chemotherapy with 4 cycles of EC (epirubicin plus cyclophosphamide) every 3 weeks followed by 4 cycles of docetaxel every 3 weeks. Patients received concurrent trastuzumab (8 mg/kg IV loading dose followed by 6 mg/kg) every 3 weeks from cycle 1 of EC. Following surgery all patients completed trastuzumab treatment for 1 year. The pathological complete response rate (pCR) was 30.3% and 63.6% had breast conserving surgery.r
In the NOAH trial, 228 patients with HER-2 positive locally advanced or inflammatory breast cancer were randomly assigned to neoadjuvant trastuzumab concurrent with chemotherapy followed by adjuvant trastuzumab (to complete one year of treatment) or neoadjuvant chemotherapy alone. The neoadjuvant chemotherapy regimen consisted of 3 cycles of AT (doxorubicin plus paclitaxel) every 3 weeks, followed by 4 cycles of paclitaxel every 3 weeks, and then 3 cycles of CMF (cyclophosphamide, methotrexate, and fluorouracil ) every 4 weeks. Patients receiving neoadjuvant trastuzumab compared to chemotherapy alone had a significantly improved pCR rate (43% v 23%) and three-year event-free survival (71% v 56%). With median follow-up of 3.2 years, there was no significant difference in OS (87% v 79%).r
In the GeparQuattro trial, the subset of 445 HER-2 positive patients with operable or locally advanced breast cancer received neoadjuvant trastuzumab concurrent with one of three randomly assigned neoadjuvant chemotherapy regimens, followed by adjuvant trastuzumab to complete one year of therapy. All patients received 4 cycles of epirubicin and cyclophosphamide then were randomized to either 4 cycles of docetaxel, 4 cycles of docetaxel concomitantly with capecitabine, or 4 cycles of docetaxel followed by 4 cycles of capecitabine. The pCR rate was 31.7% and the breast conserving surgery rate was 63%.r
A meta-analysis including 5 trials and 515 patients randomised to trastuzumab plus neoadjuvant chemotherapy or neoadjuvant chemotherapy alone found probability of achieving pCR was higher for the trastuzumab plus chemotherapy arm (RR 1.85, 95% CI 1.39-2.46; p<0.001) but there was no significant difference in rates of breast conserving surgery.r