Abstract
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%; p = .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.
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