Post-First Progression Use of Bevacizumab in Metastatic Colorectal Cancer (mCRC) (SAFE)

Efficacy and Safety of Second-line Combination Chemotherapy With Avastin in Patients With Metastatic Colorectal Cancer Who Have Received First-line Chemotherapy Plus Avastin

Bevacizumab beyond progression has been proven to be safe in the community setting (BRiTE) and in the post-marketing study (BEAT), and confirmed its efficacy and safety in the first line with all regimens of chemotherapy. A total of 1,953 patients were treated in BRiTE. At median follow-up of 17.5 mo, there were 1,369 1st PD and 839 deaths. Among patients with 1st PD, 65.2% received any 2nd-line chemotherapy, 34.8% received cetuximab, and 53.8% received BBP. In a multivariate analysis, Bevacizumab beyond first progression and exposure to any 2nd-line chemotherapy were independently associated with increased overall survival (both p < 0.0001). Bevacizumab beyond progression appears to be associated with longer overall in BRiTE. The investigators planned a prospective study to prove this phenomenon of bevacizumab beyond progression.

Patients should have been treated with bevacizumab plus chemotherapy as a 1st line treatment, and after 1st progression, these patients will be accrued in this study of bevacizumab plus chemotherapy as a 2nd line treatment, and the combined chemotherapy will be chosen by physician's decision in consider with previous chemotherapy.

Bevacizumab continuation plus chemotherapy in patients who have failed previous bevacizumab plus other chemotherapy

Inclusion Criteria: Histologically documented colorectal adenocarcinoma Progression during first-line bevacizumab containing chemotherapy within 3 months No serious toxicity to bevacizumab of 1st line treatment Unresectable metastases Uni-dimensional measurable lesion(s) by RECIST Age over 18 years old ECOG 0-2 Adequate organ functions by clinical laboratory exams Exclusion Criteria: Other tumor type than adenocarcinoma CNS metastases GI bleeding Hypersensitivity to any of chemotherapeutic agents Prior use of cetuximab or other targeted agents other than bevacizumab Major surgery within 6 weeks Other serious illness

Hong YS, Lee J, Kim KP, Lee JL, Park YS, Park JO, Park SH, Kim SY, Baek JY, Kim JH, Lee KW, Kim TY, Kim TW. Multicenter phase II study of second-line bevacizumab plus doublet combination chemotherapy in patients with metastatic colorectal cancer progressed after upfront bevacizumab plus doublet combination chemotherapy. Invest New Drugs. 2013 Feb;31(1):183-91. doi: 10.1007/s10637-012-9853-3. Epub 2012 Jul 11.