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Background  Trifluridine and tipiracil (FTD + TPI) and regorafenib (REG) are approved treatments for the treatment of refractory metastatic colorectal cancer (mCRC). This study assesses adherence and duration of therapy with FTD + TPI versus REG and explores the effect of sequencing on adherence.    Materials and Methods  Adults diagnosed with mCRC were identified in the IQVIA Real‐World Data Adjudicated Claims: U.S. database (October 2014–July 2017). The observation period spanned from the index date (first dispensing of FTD + TPI or REG) to the earliest of a switch to another mCRC agent, the end of continuous enrollment, or the end of data availability. Medication possession ratio (MPR), proportion of days covered (PDC), and persistence and time to discontinuation (gap ≥45 days) were compared between FTD + TPI and REG users and among switchers (FTD + TPI‐to‐REG vs. REG‐to‐FTD + TPI).    Results  A total of 469 FTD + TPI and 311 REG users were identified. FTD + TPI users had higher compliance with an MPR ≥80% (odds ratio [OR], 2.47;  p  &lt; .001) and PDC ≥80% (OR, 2.77;  p  &lt; .001). FTD + TPI users had better persistence (82.8% vs. 68.0%;  p  &lt; .001) and lower risk of discontinuation (hazard ratio [HR], 0.76;  p  = .006). Among switchers (96 FTD + TPI‐to‐REG; 83 REG‐to‐FTD + TPI), those switching from FTD + TPI to REG were more likely to have an MPR ≥80% (OR, 2.91;  p  &lt; .001) and PDC ≥80% (OR, 4.60;  p  &lt; .001) compared with REG‐to‐FTD + TPI switchers while treated with these drugs. Additionally, FTD + TPI‐to‐REG switchers had a lower risk of first treatment discontinuation (HR, 0.66;  p  = .009).    Conclusion  FTD + TPI users had significantly higher adherence and persistence, and patients who were treated with FTD + TPI before switching to REG also had higher adherence and persistence outcomes.    Implications for Practice  Trifluridine plus tipiracil (FTD + TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) but have different tolerability profiles. This study assessed real‐world adherence to treatment with FTD + TPI versus REG and compared outcomes among patients who switched from FTD + TPI to REG and vice versa. FTD + TPI was associated with significantly higher medication adherence and longer time to discontinuation than REG. Patients treated with FTD + TPI prior to switching to REG also showed higher adherence outcomes. Findings could help inform decision making regarding the choice and sequencing of treatment with FTD + TPI versus REG in patients with mCRC.

Real‐World Adherence in Patients with Metastatic Colorectal Cancer Treated with Trifluridine plus Tipiracil or Regorafenib