[Regorafenib versus S-1 plus Bevacizumab for Metastatic Colorectal Cancer as Salvage Line-A Phase II Study (OGSG1301)].

Background Regorafenib(Rego)is the salvage line standard treatment for metastatic colorectal cancer(mCRC), which often causes severe toxicities, such as hand-foot syndrome. Previously, we reported that in phase Ⅱ study, S-1 plus bevacizumab( Bev)(SB)showed favorable anticancer activity and feasibility as a salvage line. The aim of this study was to evaluate 2 treatments for mCRC as salvage line. Patients and methods In this multicenter phase Ⅱ study, the patients were randomly assigned(1:1)to the Rego or SB group. In the Rego group, Rego 160 mg/kg body weight was orally administered every 28 days for 21 days. In the SB group, S-1 was orally administered every 42 days for 28 days, according to body surface area, and Bev 5 mg/kg was administered by intravenous infusion on days 1, 15, and 29. Administration of S-1 every 21 days for 14 days and Bev 7.5 mg/kg on day 1 was also permitted. The primary endpoint was overall survival(OS), and the planned sample size was 86. Results This study was ended prematurely due to poor accrual. Overall, 8 patients were enrolled from 6 institutions between Oct 2013 and May 2015. Although 4 patients were assigned to each group, one patient in the Rego group was excluded after enrollment. The median OS in the Rego and SB groups was 30.2 months and 6.6 months, respectively(hazard ratio: 0.205, p=0.123). The median progression-free survival in the Rego and SB groups was 3.7 months and 1.6 months, respectively. The disease control rate in the Rego and SB groups was 100% and 75%, respectively. The Grade 3 or 4 adverse events were increased, including AST/ALT(n=1, 25%), hyponatremia(n=1, 25%), hand-foot syndrome(n=1, 25%), hypertension(n=1, 25%), and proteinuria(n=1, 25%)in the Rego group and colitis( n=1, 25%)in the SB group; the treatment was discontinued. Conclusion Despite the fact that data could only be collected from a small number of patients, SB is not recommended as salvage line for mCRC.