The impacts of initiating regorafenib with reduced dose on treatment outcomes in metastatic colorectal cancer.

133 Background: Since the results of the ReDOS study were published, starting regorafenib (REG) at a reduced dose is now considered a treatment option for patients with metastatic colorectal cancer (mCRC). However, the impact of starting REG at a reduced dose on treatment outcomes in the real-world setting has not been fully investigated. Methods: We retrospectively analyzed patients who received REG for mCRC at 4 institutions between May 2013 and December 2020. These patients were divided into two groups: those who started REG before (Period A) and after (Period B) the ReDOS study publication (May 2018). The treatment outcomes between Period A and B were compared in this analysis. Results: A total of 573 patients were evaluated (385 in Period A and 188 in Period B, respectively). In Period B, significantly more patients started REG with reduced dose (34.3% vs. 75.5%, p< 0.001). The median time to first dose reduction was 32.0 days [95% CI: 29.1-34.9] in Period A and 61.0 days [95% CI: 33.7-88.9] in Period B, which was significantly longer in Period B (HR = 0.685, p= 0.003). Both any grades and ≥grade3 hand foot skin reaction (HFSR) were significantly less frequent in Period B than in Period A (any grades: 65.5% vs 54.8%, p= 0.017, ≥grade3: 21.3% vs 14.4%, p= 0.054). The median time to onset of any grades HFSR was 16.0 days [95% CI: 13.6-18.4] in Period A and 28.0 days [95% CI: 15.6-40.4] in Period B, which was significantly longer in Period B (HR = 0.738, p= 0.007). The median overall survival was 6.7 months [95% CI: 5.9-7.4] in Period A, and 5.4 month [95% CI: 4.3-6.5] in Period, respectively (HR = 1.105, p= 0.281). The median progression free survival was 2.0 months [95% CI: 1.9-2.1] in Period A and 2.1 months [95% CI: 1.8-2.4] in Period B, respectively (HR = 1.064, p= 0.498). Conclusions: Our results suggest that starting REG at a reduced dose may contribute to reducing the frequency and delaying the onset of HFSR, whereas it may not affect efficacy.