Association of Hand-Foot Skin Reaction with Regorafenib Efficacy in the Treatment of Metastatic Colorectal Cancer

<b><i>Purpose:</i></b> Hand-foot skin reaction (HFSR) can deteriorate quality of life in patients receiving regorafenib. Cutaneous toxicity is a main adverse effect of multikinase inhibitors and has also been associated with clinical outcome. This study assessed the association between the antitumor efficacy of regorafenib and HFSR in patients with metastatic colorectal cancer (mCRC). <b><i>Methods:</i></b> Patients who received regorafenib at 160 mg/day during the first 3 weeks of each 4-week cycle were divided into subgroups based on whether they developed HFSR between May 2013 and October 2015. Estimates of overall survival and progression-free survival were calculated using the Kaplan-Meier method. <b><i>Results:</i></b> Ninety-seven patients received at least one dose of regorafenib in this retrospective study. Of these patients, 81.4% (<i>n</i> = 79) experienced HFSR of any grade, and 34.0% (<i>n</i> = 33) had grade 3 HFSR. Among those patients with HFSR at any time during the study, 68.0% (<i>n</i> = 66) underwent the first HFSR event (any grade) during cycle 1. Both overall survival and progression-free survival were improved in patients who had HFSR grade ≥2 at any time compared with those who had HFSR grade ≤1. Multivariate logistic regression analysis revealed a history of HFSR grade ≥2 induced by capecitabine as a significant risk factor for severe HFSR (grade ≥2). <b><i>Conclusions:</i></b> Patients with mCRC treated using regorafenib who experienced severe HFSR showed better overall survival than patients without severe HFSR. Severe HFSR may offer an early surrogate marker for the efficacy of regorafenib in patients with mCRC.