Randomized phase III study of trastuzumab, paclitaxel, and carboplatin versus trastuzumab and paclitaxel in women with HER-2 overexpressing metastatic breast cancer: An update including survival

Abstract

573 Purpose: This randomized multicenter phase III trial evaluated the efficacy and safety of trastuzumab with paclitaxel 175 mg/m2 and carboplatin AUC=6 (TPC) versus trastuzumab with paclitaxel 175 mg/m2 (TP) in women with HER-2 overexpressing metastatic breast cancer. Methods: Between November 1998 and May 2002, 196 patients (pts) with HER-2 overexpression of 2+ or 3+ by immunohistochemistry were randomized; 188 were eligible; 93 pts received TPC and 95 pts received TP. In both arms, chemotherapy was delivered every 3 weeks for at least 6 cycles and weekly trastuzumab until progression. Results: Overall response (OR) and time to progression (TTP) were significantly improved with TPC compared to TP; OR for TPC was 52%, compared to 36% for TP (P = .04). Median TTP was 11.9 months for TPC and 6.8 months for TP (P = .02). This improvement was greater in HER2 3+ pts, with OR of 57% versus 37% (P = .03), and median TTP of 14.6 months vs 6.9 months (P = .006), for TPC and TP, respectively. There was a trend in the overall survival in favor of TPC of 42.1 months compared to TP with 33.3 months (P= 0.27); in IHC 3+ patients median OS of 42.1 months for TPC vs 30.6 months for TP (P=0.11). Therapy was well tolerated on both arms of the study. Grade 3/4 neutropenia and thrombocytopenia were more common with TPC, as expected. There was no difference in fever/neutropenia, neuropathy, fatigue, and other toxicities between study arms. There was one case of congestive heart failure, seen in the TP arm. Conclusion: The addition of carboplatin to paclitaxel and trastuzumab significantly improved response rate and TTP in pts with a trend to improved overall survival with HER-2 overexpressing metastatic breast cancer. Treatment was well tolerated. Supported by Bristol-Myers Squibb, Plainsboro, NJ. and Genentech, South San Francisco, CA, USA Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Study support with grants for clinical trials from Bristol-Myers Squibb; clinical trial support from Aventis; clinical trial support from Eli Lilly Bristol-Myers Squibb Bristol-Myers Squibb