Sidedness and addition of chemotherapy associated with treatment outcomes of regorafenib for metastatic colorectal cancer: a population-wide cohort study

•The outcome of regorafenib use for mCRC in this population-wide cohort is consistent with previous trials.•Both left-sidedness and the addition of chemotherapy were positive prognostic factors of regorafenib treatment for mCRC.•An interaction between tumor sidedness and KRAS status existed in the multivariate model of regorafenib treatment outcome. BackgroundRegorafenib is a salvage option for metastatic colorectal cancer (mCRC). Understanding the prognostic factors for mCRC patients undergoing regorafenib treatment can help optimize therapeutic strategies.Materials and methodsWe searched Taiwan's National Health Insurance database for patients who began regorafenib treatment for mCRC between 1 September 2015 and 31 December 2018. Taiwan's National Death Registry and the Taiwan Cancer Registry were examined for data on survival and clinicopathological variables, respectively.ResultsIn total, 3643 patients were included in the analysis. The median time to treatment discontinuation (TTD) was 2.3 months, and the median overall survival (OS) was 7.2 months. Compared with the patients with a right-sided tumor, those with a left-sided primary tumor exhibited a significantly longer TTD (2.4 versus 2.1 months, P < 0.001) and OS (7.6 versus 6.1 months, P < 0.001). The patients who received chemotherapy with regorafenib also exhibited a longer TTD (2.6 versus 2.2 months, P < 0.001) and OS (8.3 versus 6.7 months, P < 0.001) than did the patients who did not. In multivariate analysis, left-sidedness and chemotherapy addition were confirmed as predictors of longer TTD and OS. Because of the interaction between sidedness and KRAS mutation, we established separate Cox models and identified that left-sidedness was an independent predictor of longer TTD and OS for KRAS wild-type tumors but not for KRAS-mutant tumors.ConclusionsIn this population-wide cohort study, left-sidedness of the primary tumor and the addition of chemotherapy were associated with a longer OS and TTD for regorafenib treatment for mCRC. Regorafenib is a salvage option for metastatic colorectal cancer (mCRC). Understanding the prognostic factors for mCRC patients undergoing regorafenib treatment can help optimize therapeutic strategies. We searched Taiwan's National Health Insurance database for patients who began regorafenib treatment for mCRC between 1 September 2015 and 31 December 2018. Taiwan's National Death Registry and the Taiwan Cancer Registry were examined for data on survival and clinicopathological variables, respectively. In total, 3643 patients were included in the analysis. The median time to treatment discontinuation (TTD) was 2.3 months, and the median overall survival (OS) was 7.2 months. Compared with the patients with a right-sided tumor, those with a left-sided primary tumor exhibited a significantly longer TTD (2.4 versus 2.1 months, P < 0.001) and OS (7.6 versus 6.1 months, P < 0.001). The patients who received chemotherapy with regorafenib also exhibited a longer TTD (2.6 versus 2.2 months, P < 0.001) and OS (8.3 versus 6.7 months, P < 0.001) than did the patients who did not. In multivariate analysis, left-sidedness and chemotherapy addition were confirmed as predictors of longer TTD and OS. Because of the interaction between sidedness and KRAS mutation, we established separate Cox models and identified that left-sidedness was an independent predictor of longer TTD and OS for KRAS wild-type tumors but not for KRAS-mutant tumors. In this population-wide cohort study, left-sidedness of the primary tumor and the addition of chemotherapy were associated with a longer OS and TTD for regorafenib treatment for mCRC.