Sidedness and addition of chemotherapy associated with treatment outcomes of regorafenib for metastatic colorectal cancer (mCRC).

Abstract

36 Background: Regorafenib is one of the options of salvage treatment for mCRC. We aimed to explore the prognostic factors of such regorafenib treatment. Methods: We searched the database of National Health Insurance, Taiwan for patients who initiated regorafenib treatment for mCRC from September 1, 2015, to December 31, 2018. Database interrogation of National Death Registry, Taiwan and Taiwan Cancer Registry was conducted for survival data and clinicopathological variables, respectively. Results: A total of 3,643 patients were included in the analysis. The median age was 61.2 years. The primary tumor was left-sided and KRAS mutant in 75.3% and 54.5% of patients, respectively; 28.9% of patients received chemotherapy simultaneously, with irinotecan as the most common companion. The median time to treatment discontinuation (TTD) was 2.3 months (95% confidence interval [CI]: 95% CI: 2.3-2.3), and the median overall survival (OS) was 7.2 months (95% CI: 6.9-7.4). Patients with left-sided primary tumors, compared with patients with right-sided tumors, exhibited significantly longer TTD (median, 2.4 vs. 2.1 months, p < 0.001) and OS (median, 7.6 vs. 6.1 months, p < 0.001). By contrast, TTD and OS of patients under regorafenib treatment were similar regardless the KRAS mutation status ( p = 0.415 and 0.643, respectively). Patients who received chemotherapy along with regorafenib, compared with patients who did not, also exhibited significantly longer TTD (median, 2.6 vs. 2.2 months, p < 0.001) and OS (median, 8.3 vs. 6.7 months, p < 0.001). In multivariate analysis adjusting age, sex, time from colorectal cancer diagnosis, hospital level, KRAS mutation, and initial regorafenib dose, left-sidedness of the primary tumor remained a predictor for better TTD (hazard ratio [HR]: 0.88, p = 0.002) and OS (HR: 0.92, p = 0.048), as well as addition of chemotherapy (for TTD, HR: 0.86, p < 0.001; for OS, HR: 0.76, p < 0.001). Due to the interaction between sidedness and KRAS mutation, we established separate Cox models and found that left-sided primary tumor was an independent predictor for better TTD and OS for KRAS wild-type tumors, but not for KRAS mutant tumors. Conclusions: In this population-wide cohort study, left-sided primary tumor and addition of chemotherapy were associated with better TTD and OS of regorafenib treatment for mCRC.