Initial safety results from a randomized, phase II study of high-risk colorectal cancer patients (stage IIIC) treated with either regorafenib or standard of care (no treatment) after adjuvant FOLFOX.

Abstract

e15152 Background: Standard adjuvant therapy for colorectal cancer (CRC) is fluoropyrimidine or FOLFOX. The stage IIIC relapse rate is high with a median 5 year survival of only 28%. The multi-kinase inhibitor regorafenib has shown significantly improved overall survival (OS) versus placebo in 3rd-line+ metastatic CRC patients (pts) in 2 phase III trials. We explore whether adding regorafenib to standard adjuvant therapy is able to reduce the high relapse rates in stage IIIC CRC pts. Methods: This study compares efficacy and safety of adjuvant FOLFOX +/- 6 cycles of regorafenib in IIIC CRC pts. Study endpoints include: finding the starting dose of regorafenib that allows ≥75% pts to complete therapy after adjuvant FOLFOX. The first 50 pts are being randomly assigned to either 120 or 160 mg of regorafenib daily for 3 weeks followed by 1 week of rest for a total of 6 cycles. We report the initial safety results on the first 24 pts treated. 6 pts discontinued treatment; 2 received 120 mg and 4 received 160 mg Results: Of the pts completing 6 cycles of regorafenib 120 mg vs 160 mg, the most common grade 3 toxicities were hypertension (0 vs. 30%), rash (10 vs.30%), and lipase elevation (0 vs 10%). No grade 4 or 5 toxicities were observed. Conclusions: The interim analysis reveals no increased toxicities from the addition of regorafenib at either 120 mg or the approved dose (160 mg), to adjuvant FOLFOX. Toxicities observed were mostly grade 1 or 2 and medically manageable. No safety signals have been identified. This study continues to enroll pts. Clinical trial information: NCT02425683.