PD-0004 Perioperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer; A Multicenter, Single Arm Phase I/II Trial: Asso Lm1

Abstract

ABSTRACT Introduction Patients with colorectal cancer (CRC) and liver metastases may benefit from pre- and postoperative chemotherapy and disease resection. Best treatment sequence, length and combination still needs to be determined. We evaluated Bevacizumab and XELOX in a multicenter approach. Resectabilty was the primary endpoint, periOP morbidity, response rate, recurrence-free and overall survival the secondary end points. Methods Patients with liver metastases from CRC potentially curable by resection were eligible for this trial. Patients received Bevacizumab 5mg/kg (day 1), oxaliplatin 85mg/m2 (day 1) and Capecitabine 3000mg/m2/day (days 1–7) of a 2-week cycle for six cycles. The sixth cycle did not include Bevacizumab, resulting in 5 weeks between the last Bevacizumab dose and surgery. Therapy with Bevacizumab plus XELOX was restarted 5 weeks after surgery for another six cycles. Response rates were assessed by the PIs and after central review, pathological response was assessed centrally according to Rubbia-Brandt. Results 43 patients (pts) with a median age of 66 years (38-80) were enrolled into this multicenter trial. 78% of these pts had synchronous disease, 51% of these started treatment without primary tumor resection. The median number of metastases was 2 (1-10) and median Fong score was 3 (0-4). In total of 8 pts were ineligible for resection, 1 due to PD, 7 due to protocol violation or personal reason. Resectability of operated patients was 97% with 34 R0 resections and one R1 resection. Postoperative morbidity occurred in 22% of the pts, 3 operative revisions were related to the primary tumor resection. Efficacy results for response in 38 eligible patients confirm an ORR of 66%, 31% SD and 3% PD according to RECIST. Preoperative grade 3/4 adverse events were 17% diarrhea, 5% HFS, 2% neuropathy and 5% thromboembolic events. Histological assessment of resected metastases revealed a major histological response in 56%, a partial histological response in 28%, and no histological response in 16%. Recurrence-free (RFS) and overall survival (OS) significantly differed dependent upon the fulfillment of the adjuvant treatment cycles in curative resected patients (24 pts completed periOP CTx vs 10 pts neoCTx only): median RFS was 26.2 months in patients receiving postsurgical Bev + Xelox vs. 7.4 months in those without postOP therapy (p Conclusion These data demonstrate that Bevacizumab and XELOX provide substantial response rates with well-known adverse events in this potentially curative mCRC setting. In patients eligible for resection after 3 months of neoadjuvant therapy perioperative morbidity is not increased compared to studies without Bevacizumab. Long-term recurrence-free and overall survival was significantly prolonged in our study in patients receiving postoperative chemotherapy plus Bevacizumab.