ReDOS: Regorafenib Dose-Escalation Strategy in Refractory Advanced Colorectal Cancer


Key Points

  • A greater proportion of patients in the dose-escalation group started the third cycle of treatment.
  • The dose-escalation strategy compared favorably with standard dosing in safety and activity profiles.

In the phase II ReDOS trial reported in The Lancet Oncology, Bekaii-Saab et al found that a regorafenib dose-escalation strategy compared favorably with standard dosing in regard to toxicity profile and activity in patients with refractory advanced colorectal cancer.   

Study Details

The open-label trial included 116 evaluable patients from 39 U.S. sites with advanced disease refractory to previous standard therapy, including EGFR inhibitors if KRAS wild-type. Patients were randomly assigned between June 2015 and June 2017 to a regorafenib dose-escalation strategy (starting dose 80 mg/day with weekly escalation in a 40 mg increment to 160 mg/day if no significant drug-related adverse events occurred; n = 54) or a standard-dose strategy (160 mg/day) for 21 days of a 28-day cycle (n = 62).

The primary outcome measure was proportion of patients starting the third cycle of regorafenib.  Superiority for dose escalation was achieved if the one-sided P value was < .2.

Treatment Outcomes

Median follow-up was 1.18 years. Initiation of three cycles of treatment was achieved by 23 patients (43%) in the dose-escalation group vs 16 patients (26%) in the standard-dose group (one-sided P = .043). The frequency of grade 3 adverse events commonly associated with regorafenib—including fatigue, hand-foot skin reaction, hypertension, and diarrhea—was generally lower in the dose-escalation group in the first two cycles of treatment. Overall, the most common grade 3 or 4 adverse events were fatigue (13% in the dose-escalation group vs18% in the standard-dose group), hand-foot skin reaction (15% vs 16%), abdominal pain (17% vs 6%), and hypertension (7% vs 15%). Drug-related serious adverse events occurred in six vs eight patients. One death—due to myocardial infarction in a standard-dose patient—was considered probably related to treatment.

Median overall survival was 9.8 months in the dose-escalation group vs 6.0 months in the standard-dose group (hazard ratio [HR] = 0.72, P = .12) and median progression-free survival was 2.8 months vs 2.0 months (HR = 0.84, P = .38).

The investigators concluded, “The dose-escalation dosing strategy represents an alternative approach for optimizing regorafenib dosing with comparable activity and lower incidence of adverse events, and could be implemented in clinical practice on the basis of these data.”

Tanios Bekaii-Saab, MD, of the Mayo Clinic, Scottsdale, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Bayer HealthCare Pharmaceuticals. For full disclosures of the study authors, visit

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