Long-term outcome of phase II study of biweekly dose-dense AC followed by weekly paclitaxel and carboplatin and trastuzumab (TC ± H) based on HER2 status in large and inflammatory breast cancer (BC).

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680 Background: We reported high pathologic complete response (pCR) with TC±H as salvage or consolidative treatment following anthracyclines in a pilot and a confirmatory phase II trial (SABCS2004-ASCO 2009). Methods: 47 of 48 enrolled women with BC received weekly TC for 9-12 weeks, and concurrent 12-16 weekly H (if HER2–positive) following 2-4 cycles of dose-dense AC. The clinical response, pCR rates and early survival outcomes were reported previously. Results: In 35 patients (pts) with stage II-III BC, higher pCR rates occurred in pts with HER2-positive tumors (80% vs. 32% for HER2-negative tumors; p > 0 .008), with ER–negative tumors (94% vs. 16% for ER-positive tumors; p < 0.0001), or with triple-negative tumors (100% vs. 13% ER-positive and HER2-negative tumors; p > 0.001); at a median of 54 months postoperatively, recurrence-free survival (RFS) was 94%, and distant RFS (DRFS) was 97%, and at a median of 60 months from diagnosis, overall survival (OS) was 97% (95% CI 91-100). In 15 pts with HER2-positive BC, RFS and OS is 100%, versus 90% and 95%, respectively in 20 with HER2- negative BC (log-rank p > 0.22 and 0.39). For comparison, in 13 pts with stage II-III BC in the pilot study, RFS, DRFS and OS were 77% (includes contra-lateral BRCA-associated primary), 85%, and 92% at median of 80 months. At five years, combining pilot and phase-II data (n=48), RFS and OS is similar at 96% for 22 patients with HER2-positive and 26 with HER2-negative breast cancer (p > 0.91). Importantly, of 22 HER2-positive patients, only 2 completed ≥ 6 months of trastuzumab. Though 5 pts with metastasis achieved pCR, RFS and OS at 5 years is 8% and 25% in phase II study (n > 12) and 0% in the pilot study (n > 4). Conclusions: Despite inclusion of inflammatory BC, neoadjuvant weekly carboplatin and paclitaxel with trastuzumab (in HER2-postive) following response-adjusted dose-dense anthracyclines achieves high long-term survival in patients with HER2-positive and HER2-negative BC. Moreover, RFS and OS in HER2-positive are similar to that in HER2-negative BC, despite use of short course of trastuzumab. Long-term survival in metastatic setting remains dismal. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Berlex