Regorafenib is suitable for advanced colorectal cancer patients who have previously received trifluridine/tipiracil plus bevacizumab

Abstract

Regorafenib is a standard salvage line therapy used for advanced colorectal cancer (CRC). Recently, trifluridine/tipiracil (TFTD) plus bevacizumab also showed promising efficacy as a salvage line therapy for advanced CRC. However, the efficacy and safety of regorafenib for patients with advanced CRC who have previously received TFTD plus bevacizumab is unclear. We retrospectively collected clinicopathologic data from patients with advanced CRC who received regorafenib after TFTD plus bevacizumab in multiple institutions between April 2017 and June 2020.Thirty-four advanced CRC patients who received regorafenib were analyzed. The median age was 66.5 (range 43–81 years), 11 patients were male, and all had an ECOG performance status(PS) of 0 or 1. Twenty-two patients had left-sided tumors, 18 patients had RAS mutants, and 1 patient had a BRAF V600E mutation. The response rate was 0%, and the disease control rate was 31%. The median progression-free survival was 70 days (95% CI: 56–91), and the overall survival was 233 days (95% CI: 188–324). Treatment was discontinued in 32 patients, and 28 (82%) discontinued treatment due to progressive disease. The major grade 3 and4 toxicities were proteinurea (29%), hypertension (26%), hand-foot syndrome(15%), and platelet decrease (6%). Regorafenib after TFTD plus bevacizumab showed efficacy similar to that of the previous study, and no new adverse events were observed.

Treatment Settings and Outcomes with Regorafenib and Trifluridine/Tipiracil at Third-Line Treatment and beyond in Metastatic Colorectal Cancer: A Real-World Multicenter Retrospective Study

“…However, because of differences among cases and the presence of several molecular subtypes, evaluating therapy alternatives is difficult, and in the setting of varying tolerance profiles against minor improvements in overall survival and progression-free survival, T and R are still regarded by some as clinically unimportant [ 25 , 26 , 27 , 28 ]. The best protocols for the administration of T and R in patients with advanced disease, the identification of subpopulations that might benefit from vital treatment with these drugs, and the identification of those subpopulations that might benefit from treatment with these drugs vs. the best supportive therapy alone are all questions that have yet to be resolved [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Furthermore, T and R have not been directly compared to one another, and it is uncertain which agent should be given first [ 36 , 37 , 38 , 39 , 40 , 41 ].…”

Role and Function of Receptor Tyrosine Kinases in BRAF Mutant Cancers

“…In terms of metastatic CRC, regorafenib is clinically applied as a therapy for pre-treated patients with progressive disease after two phase 3 clinical trials (CORRECT and CONCUR studies) from 2013 and 2015 revealed significantly prolonged overall survival [182,183]. Notably, regorafenib also showed activity as a second-line therapy in patients with advanced CRC pre-treated with bevacizumab plus trifluridine/tipiracil [184]. Meanwhile, the dual RAF/VEGFR2 inhibitor RAF265 has undergone a first-in-human phase 1 clinical trial with melanoma patients.…”