Bekaii-Saab TS, et al. - In view of the limited use of regorafenib due to its adverse event profile despite an overall survival benefit in patients with refractory metastatic colorectal cancer, researchers examined two regorafenib dosing schedules for the safety and activity. In this randomized, multicenter, open-label, phase 2 study, they randomly assigned 123 adults aged 18 years or older (1:1:1:1) with histologically or cytologically confirmed advanced or metastatic adenocarcinoma of the colon or rectum into four groups with two distinct regorafenib dosing strategies and two clobetasol usage plans, stratified by hospital. Strategies used for administering regorafenib were a dose-escalation strategy (starting dose 80 mg/day orally with weekly escalation, per 40 mg increment, to 160 mg/day regorafenib) if no significant drug-related adverse events occurred and a standard-dose strategy (160 mg/day orally) for 21 days of a 28-day cycle. Either pre-emptive or reactive clobetasol usage plans (0.05% clobetasol cream twice daily applied to palms and soles) were applied. There were 54 patients in the dose-escalation group and 62 in the standard-dose group. Outcomes establish the utility of the dose-escalation dosing strategy as an alternative approach for optimizing regorafenib dosing with similar activity and lower incidence of adverse events and support the implementation of this strategy in clinical practice.