Surgical Complications and the Use of Neoadjuvant Bevacizumab.

Introduction:Neoadjuvant chemotherapy is being increasingly used in operable breast cancer. There are limited data on the safety of bevacizumab (Bev) in combination with chemotherapy in the neoadjuvant setting. We sought to explore the safety and efficacy of neoadjuvant cisplatin/Bev in a protocol for triple negative breast cancer (TNBC), with post operative dose dense AC or AC/Taxol plus Bev. We present our operative experience, including postoperative complications. We also compared this to a smaller single arm neoadjuvant cisplatin alone study.Methods:51 patients with confirmed TNBC provided informed consent and were enrolled in a single arm phase II trial of neoadjuvant cisplatin 75 mg/m 2 plus Bev15 mg/kg q 3 weeks x 3 cycles with the 4 th cycle cisplatin alone prior to definitive surgery. This design allowed at least 6 weeks between the last dose of Bev and surgery. Research biopsies were obtained before treatment and at surgery. Postoperatively, patients received doxorubicin and cytoxan (AC) plus bevacizumab or AC/Taxol plus Bev. Median age was 50 yrs (range 30-65 yrs); tumors were clinical stage II 48 (94%) and stage III 3 (6%).28 patients with confirmed TNBC were enrolled in our phase II trial of neoadjuvant cisplatin. Single-agent cisplatin 75mg/m 2 q3weeks x 4cycles was given prior to definitive surgery. Median age was 50 yrs (range 29-69yrs); tumors were clinical stage II (75%), stage III (25%). Postoperatively, patients received AC or AC/Taxol. Two-sided Fisher exact test were used for comparing the 2 trials.Results:Fifty-one patients received neoadjuvant protocol therapy with cisplatin/Bev (all received at least one cycle of bevacizumab, 7 did not complete all cycles of preop bevacizumab) and underwent definitive local therapy to the breast. Breast conserving therapy was performed in 29 (57%) and mastectomy with or without reconstruction in 22 (43%). Postoperative complications were reported in 22 (43%) of patients: 4 (8%) required wound debridement and explantation of expanders, 8 (16%) wound breakdowns, 5 (10%) developed hematomas requiring operative intervention and 5 (10%) seromas requiring multiple aspirations.Twenty-eight patients completed neoadjuvant cisplatin therapy and underwent definitive local therapy to the breast. Breast conserving therapy was performed in 13 (46%) and mastectomy with or without reconstruction in 16 (54%). Postoperative complications were reported in 11 (39%) of patients: 5 seromas requiring drainage (18%), 2 hematomas (7%), 2 abscesses (7%), and 2 (7%) wound breakdowns. No reconstructions were lost including the 3 expanders and 2 TRAM flaps.We compared all toxicities between the two trials, (p= 0.81 NS), and wound healing related complications between the two trials (p= 0.10 NS).Conclusions:Cisplatin/Bevacizumab and cisplatin alone neoadjuvant therapy resulted in a significant number of postoperative complications. Specifically use of expanders or implants may be problematic for patients treated with Bev with a trend towards more wound related events for this group. However, this was a single arm trial, a randomized controlled studies will be necessary in determine the optimal use of bevacizumab in the timing of breast cancer surgery. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 43.