A pilot study of adjuvant bevacizumab and chemotherapy after neoadjuvant chemotherapy for high-risk breast cancer.
J Clin Oncol 26: 2008 (May 20 suppl; abstr 519)
E. L. Mayer, K. D. Miller, H. S. Rugo, J. M. Peppercorn, L. A. Carey, N. Ryabin, K. Josephs, E. P. Winer, H. J. Burstein
Background: Patients (pts) with residual breast cancer after neoadjuvant chemotherapy are at increased risk of recurrence, and may have chemotherapy-resistant disease. We sought to explore adjuvant antiangiogenic therapy combined with two different chemotherapy regimens in this population.
Methods: Eligible pts had stage II-III breast cancer with residual invasive carcinoma at surgery following anthracycline-containing neoadjuvant chemotherapy. Treatment consisted of bevacizumab (B) 15 mg/kg every three weeks (1 cycle) for one year, starting no less than 1 month after surgery or 2 weeks after radiation. Sequential cohorts also received concurrent chemotherapy, either metronomic chemotherapy (CM): cyclophosphamide 50 mg PO qd, and methotrexate 2.5 mg PO d 1-2 each week for a total of 6 months, or capecitabine (X) 2,000 mg/m2/day 14d on/7d off for 18 weeks. Concurrent endocrine and/or trastuzumab therapy was allowed. The primary endpoint was feasibility and tolerability of the combination therapy. Results: 81 pts were treated with B + CM or B + X. Median age was 48y, 59% were stage III, 62% were hormone receptor positive, and 11% were HER2+. To date, the median number of cycles completed is 10 of a planned 17, with 12 pts completing treatment and 2 pts choosing to end treatment early. At a median on-study follow-up of 7.5 months, 6 pts (7%) have had tumor recurrence. Treatment-related toxicities include fatigue (41%), headache (32%), arthralgias (31%), and hypertension (23%). Preliminary analysis suggests B + CM has a more favorable side effect profile, as B + X led to more diarrhea, hand-foot syndrome, and grade 3/4 toxicity. 9 patients came off study for toxicity, including one patient with heart failure. Definitive feasibility/safety data and preliminary correlative studies will be available by June 2008. Conclusions: Adjuvant B + chemotherapy after neoadjuvant chemotherapy appears tolerable and feasible with side effects including fatigue, headache, arthralgias, and hypertension. The addition of X appears to contribute more toxicity. As previously demonstrated in our study of B monotherapy (Mayer et al, ASCO 2007, #561), the post- preoperative chemotherapy population remains high risk and merits novel therapies