P3-14-31: Preoperative Chemotherapy and Bevacizumab for Locally Advanced HER-2 Negative Breast Cancer Followed by Prolonged Postoperative Bevacizumab for Those with Less Than Complete Pathologic Response.
Authors: Carpenter JT , Forero A , Falkson CI , Nabell LM , De Los Santos JF , Krontiras H , Bland KI , Li Y 
Published: June 2012

Abstract
We studied patients with locally advanced breast cancer (LABC) to evaluate 1) whether adding concurrent bevacizumab to preoperative chemotherapy (CT) would increase the pathologic complete response (pCR) rate, 2) whether a prolonged postoperative course of bevacizumab would prevent or reduce the recurrence rate in patients who did experience pCR after preoperative chemotherapy, and 3) whether use of pegylated liposomal doxorubicin would prove comparably effective to doxorubicin with less toxicity in this setting. From 3/08-12/09 32 patients with HER-2 negative operable (LABC) received sequential preoperative CT with pegylated liposomal doxorubicin 25 mg/M2 every 2 weeks X 3, paclitaxel 175 mg/M2 every 2 weeks X 3, and cyclophosphamide 60 mg/M2 every 2 weeks X 3, all with concurrent bevacizumab 10 mg/kg every 2 weeks. One patient's disease progressed by the end of CT; 1 patient withdrew after 2 cycles of treatment. All 30 remaining patients had ≥30% shrinkage of tumor at the completion of CT. Left ventricular ejection fractions on the 31 who completed CT were &gt;55% before and after completing CT; no cardiac failure was seen. Grade III toxicities included hypertension &gt;150/90 in 7 and palmar-plantar erythrodysesthesia in 1; other toxicities were grade I or II. No proteinuria was seen. Five experienced delayed wound healing after operation. Responses: 9/32 pCR in breast and axillary nodes (2/15 in ER or PR+, 7/17 in ER/PR-), and 3 pCR in breast with ≥1 positive axillary node (2 ER or PR+, 1 ER/PR-). Hormonal treatment but no further CT was given after operation. 20/21 patients with residual invasive cancer in breast or nodes started an additional year of bevacizumab 15 mg/kg every 3 weeks; 1 never started bevacizumab due to delayed wound healing- her disease recurred before starting bevacizumab and she died 22 months after diagnosis. All but 6 of these have completed the additional year of bevacizumab (1 withdrew early due to the need for 2 emergency abdominal operations); 1 experienced recurrence in lungs during bevacizumab treatment and subsequently died 24 months after starting treatment (ER+). An additional patient with initial pCR experienced recurrence in brain, then lung 18 months after starting treatment (ER/PR -). With a median followup of 26.5 months since diagnosis, 30 of 32 remain alive, 28 of 32 remain free of recurrence, and 19 of the 20 who started bevacizumab for less than pCR after operation remain free of recurrence. Concurrent bevacizumab did not appear to influence the pCR rate from preoperative CT. The pCR rate observed using pegylated liposomal doxorubicin is comparable to that obtained at UAB with sequential treatment using doxorubicin, but is less toxic. Use of bevacizumab after operation in patients with LABC who do not experience pCR from preoperative chemotherapy may decrease recurrence and appears promising. Further observation in this group and further prospective study will be of interest.
Supported by Centocor Ortho Biotech Services and by Genentech
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-31.