Optimized Dosing of Regorafenib in Patients With Metastatic Colorectal Cancer: A Practical Guide for Oncologists, Advanced Practice Providers, and Pharmacists

The multikinase inhibitor regorafenib has improved outcomes for patients with metastatic colorectal cancer (mCRC) following failure of standard therapies. However, regorafenib may be associated with treatment-emergent adverse events (TEAEs) requiring dose modifications. The regorafenib dose-optimization study (ReDOS) investigated a systematic method for titrating regorafenib up to the highest tolerable dose through a prospective evaluation of a first-cycle dose-escalation strategy, compared with standard dosing in patients with refractory mCRC. ReDOS met its primary endpoint, with more patients starting cycle 3 in the dose-escalation group (43%) vs. the standard-dose group (26%; <i>p</i> = .043). The safety profile was consistent with previous reports, and the incidence of regorafenib-related grade 3 TEAEs was generally lower in the dose-escalation group vs. the standard-dose group in cycles 1 and 2. Secondary endpoints showed that dose escalation did not negatively impact efficacy. Initiating regorafenib below the approved standard dose (160 mg/day) improves tolerability and allows health-care professionals to individualize the dose during cycles 1 and 2 without reducing overall drug exposure. This strategy provides an evidence-based guide to optimize regorafenib dosing and improve tolerability without compromising efficacy, allowing patients to remain on regorafenib for longer and potentially improve outcomes. This review provides a clinically relevant appraisal of ReDOS and the implications for patient management from the perspective of oncologists, advanced practice providers, and pharmacists.