Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial

Abstract

BACKGROUND: Complete resection of metastases can result in cure for selected patients with metastatic colorectal cancer. METHODS: First BEAT evaluated the safety of bevacizumab with first-line chemotherapy in 1914 patients. Prospectively collected data from 225 patients who underwent curative-intent surgery were analysed, including an exploratory comparison of resection rate in patients treated with different regimens. NO16966 compared efficacy of oxaliplatin-based chemotherapy plus bevacizumab or placebo in 1400 patients. A retrospective analysis of resection rate was undertaken. RESULTS: In First BEAT, 225 out of 1914 patients (11.8%) underwent curative-intent surgery at median 64 days (range 42 -100) after the last dose of bevacizumab. R0 resection was achieved in 173 out of 225 patients (76.9%). There were no surgery-related deaths and serious post-operative complications were uncommon, with grade 3/4 bleeding and wound-healing events reported in 0.4% and 1.8%, respectively. Resection rates were highest in patients receiving oxaliplatin-based combination chemotherapy (P ¼ 0.002), possibly confounded by patient selection. In NO16966, 44 out of 699 patients treated with bevacizumab (6.3%) and 34 out of 701 patients treated with placebo (4.9%) underwent R0 metastasectomy (P ¼ 0.24). CONCLUSIONS: The rate of serious post-operative complications in First BEAT was comparable to historical controls without bevacizumab. In NO16966, there were no statistically significant differences in resection rates or overall survival in patients treated with bevacizumab vs placebo.

Neoadjuvant therapy of bevacizumab in combination with oxaliplatin and capecitabine (XELOX) for patients with metastatic colorectal cancer with unresectable liver metastases: a phase II, open‐label, single‐arm, noncomparative trial

“…22,39 Furthermore, in the subpopulation with liver-only metastatic disease in the BEAT and the First BEAT studies, 15.2% of patients underwent curative-intent hepatic metastasectomy. 26,39 Other studies too found only 14% of patients 40 or none 35 eligible for surgery with a curative intent.…”

“…22,39 Furthermore, in the subpopulation with liver-only metastatic disease in the BEAT and the First BEAT studies, 15.2% of patients underwent curative-intent hepatic metastasectomy. 26,39 Other studies too found only 14% of patients 40 or none 35 eligible for surgery with a curative intent. Although differences in study design, patient selection and study regimens between studies would preclude a direct comparison, a much higher resection rate (42.2%) was observed in the present study: the resection rate observed in the present study was higher than that with the regimen XELIRI (a combination of capecitabine and irinotecan) and FOLFIRI (resection rate: 24%) 41 and regimen FOLFOX and FOLFIRI (resection rate: 35%), 31 and consistent with a previous report that demonstrated 40% conversion rate following neoadjuvant chemotherapy with oxaliplatin, bevacizumab and capecitabine.…”

Bevacizumab in combination with chemotherapy in the first-line treatment of metastatic colorectal carcinoma

“…In these cases only radical surgery offers the chance of long-term survival. The safety and efficacy of bevacizumab in preoperative setting were evaluated in a post hoc analysis of the NO16966 and First BEAT clinical trials [45]. In the group of patients with metastases limited to the liver, 12.3% of patients treated with chemotherapy plus bevacizumab (26 of 211) eventually received a R0 resection, compared with 11.6% of patients (24 of 207) treated with chemotherapy plus placebo.…”

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

“…Disease‐specific mortality of progressive CRC has decreased significantly in past decades with novel chemotherapeutic agents, such as oxaliplatin and irinotecan, and molecular targeted drugs, such as bevacizumab, a recombinant humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF) 3. Adding bevacizumab to chemotherapy significantly reduces the residual viable tumor cell volume in resected tumors and increases the proportion of patients eligible for liver metastasis resection, when compared with chemotherapy alone 4, 5…”