Earlier randomized clinical trials demonstrated that regorafenib improves survival in patients with unresectable colorectal cancer, yet it is also linked to a substantial frequency of adverse reactions. To minimize toxicity and enhance patient tolerance, this investigation evaluated body weight–based regorafenib dosing to determine an appropriate regimen. Data were drawn from a comprehensive national claims database in Japan. We assessed the effectiveness and safety profile of regorafenib among individuals with metastatic colorectal cancer, categorizing participants by body weight (60 kg cutoff) and median average dose (120 mg), for treatments administered between 2013 and 2018. Comparisons of overall survival (OS) and adverse event rates were performed across the defined groups. A total of 2530 Japanese patients were included (heavy weight/high dose: 513; light weight/low dose: 921; heavy weight/low dose: 452; light weight/high dose: 644). After adjustment with inverse probability treatment weighting (IPTW), the heavy-weight/high-dose group and the light-weight/low-dose group showed no meaningful differences in adverse events or OS (hazard ratio, HR = 0.97). Within the light-weight subgroup, administration of a higher average dose was associated with reduced OS (IPTW-adjusted HR = 1.21, 95% CI: 1.05–1.39). By comparison, heavy-weight patients exhibited no significant OS difference between high- and low-dose categories (IPTW-adjusted HR = 1.14, 95% CI: 0.95–1.37). The results imply that light-weight patients receiving a lower dose of regorafenib can attain safety and efficacy outcomes equivalent to those observed in heavy-weight patients given higher doses. Prospective research is required to refine individualized dosing protocols that account for each patient’s body composition and overall clinical status.
