e12115 Background: Anti-angiogenic therapy improves outcomes in cancer therapy; we hypothesized an improved outcome with the addition of bevacizumab to dose dense neoadjuvant chemotherapy (ddNAC) in the treatment of locally advanced breast cancer (LABC). Methods: We added bevacizumab to ddNAC in the pre-operative management of LABC. Eligible subjects signed an informed consent, had biopsy and radiographically confirmed stage II-III LABC and absence of major organ malfunction. ddNAC was comprised of docetaxel 35mg/M2 intravenous (IV) on days 1 and 8, capecitabine 800mg/M2 by mouth two times a day on days 1-14 and bevacizumab 15mg/kg IV repeated every 21 days for 4 cycles, followed with doxorubicin 60 mg/M2 and cyclophosphamide 600mg/M2IV with peg-filgrastim 6mg given subcutaneously on day 1, every 14 days for 4 cycles (TX/ddAC). Subsequently, subjects underwent surgery and adjuvant radiation and/or hormonal therapy as clinically indicated. The primary objective was the pathologic complete response rate (pCR). As a secondary end point, we compared the rates of pCR with our prior study of the same chemotherapy regimen without bevacizumab (n = 52). Lastly, we evaluated the safety and tolerability of the regimen. Results: 34 subjects were enrolled and 31 completed the study. Using a modified intent to treat analysis, pCR with residual in-situ carcinoma (pCRinv) was 3/31 (9.7%), total pCR 8/31 (25.8%), and residual invasive carcinoma 20/31 (64.5%). In comparison, our prior study results, presented at the 2006 San Antonio Breast Cancer Symposium, showed a pCRinv7/52 (13.5%), total pCR 27/52 (52%), and rate of residual invasive carcinoma of 25/52 (48%). Observed toxicities included hand/foot syndrome, alopecia, nausea/vomiting, mucositis, neutropenia, febrile neutropenia, nail changes and hyperlacrimation. There was one treatment related death. Conclusions: The addition of bevacizumab to chemotherapy (TX/ddAC) did not improve the observed rates of pCR. However, the role of capecitabine in the neoadjuvant setting needs to be explored further. Moreover a post hoc analysis of the efficacy of the regimen in LABC subtypes is ongoing, with biologic correlates.
Assessing the Need for Adjusted Organ-at-Risk Planning Goals for Patients Undergoing Adjuvant Radiation Therapy for Locally Advanced Breast Cancer with Proton Radiation