Started dose of regorafenib and overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): A systematic review and meta-analysis.

Abstract

131 Background: Regorafenib is one of the standards of care in pts with chemorefractory mCRC. However, high toxicity is a common reason of treatment discontinuation, interruption and dose reduction. There are conflicting results how started dose of regorafenib influence OS (REBECCA, ReDOS and ARRANGE trials). Therefore, we performed systemic review and meta-analysis to evaluate association between started dose of regorafenib and OS in pts with mCRC. Methods: We performed a search of all retrospective and prospective studies in PubMed, Embase, and Cochrane library. The search criteria included all articles and abstracts for all years before 20.08.2019. We compared the pts with standard dose (160 mg) and <160 mg at the first cycle. Primary outcome was hazard ratio (HR) for OS and 95% confidence interval (CI). Random effects were used for analysis due to potential heterogeneity of the studies. Meta-analysis was conducted by "Review Manager" Ver. 5.3. Results: We identified 6 trials – 3 prospective and 3 retrospective ones, which included 1955 pts (160 mg – 1584 and <160 mg – 571 pts). Two trials showed worsening OS in pts with dose <160 mg (Adenis et al., 2016 – HR 1.26, 95%CI 1.01-1.56 and Aljubran et al., 2019 – HR 2.25, 95%CI 0.93-5.43). Two studies showed improving OS in pts with dose <160 mg (Bekaii-Saab et al., 2018 – HR 0.72, 95%CI 0.47-1.11; Gotfrit et al., 2017 – HR 0.46, 95%CI 0.17-1.22). And two studies didn’t show any difference (Yamaguchi et al., HR 0.95, 95%CI 0.82-1.1 and Argiles et al., 2019 - HR 0.86, 95%CI 0.65-1.13). According to results of the meta-analysis there was not any difference in OS between groups with the dose 160 mg and <160 mg at the first cycle: HR 0.97, 95% CI 0.78-1.21; p = 0.79; I2 = 64. Conclusions: Started dose of regorafenib <160 mg in the pts with chemorefractory mCRC does not worsen the OS and this approach can be safely used in the daily clinical practice.