Vitale P, Zanaletti N, Famiglietti V, et al. - Researchers used a cohort of refractory metastatic colorectal cancer (mCRC) patients to test the safety and efficacy of TAS-102 and regorafenib in these cases, for eventually evaluating the optimal sequence treatment for these two drugs. In this retrospective study, 140 mCRC patients were included; 64 were treated with regorafenib and 76 received TAS-102 as first treatment. Post-progression, in the regorafenib 24 (37%) patients switched to secondary treatment with TAS-102, instead, 29 (45%) of 76 patients in the TAS-102 group switched to secondary treatment with regorafenib. In the regorafenib group (n = 64) and in the TAS-102 group (n = 76), a total of 8 (12,5%) and 17 (22,4%) patients, respectively, achieved disease control. PFS and OS were identified to be similar in both treatment groups for primary and secondary treatments. The observed AEs were mostly consistent with the known safety profiles of regorafenib and TAS-102 in prior clinical trials. Overall, this work offers more information regarding the best treatment sequence for TAS-102 and regorafenib, to be implemented in clinical practice, by comparing the activity of the two agents in a large cohort of chemo-refractory mCRC patients for the first time ever.