OBJECTIVES: CORRELATE is a prospective, observational cohort study of mCRC patients treated with regorafenib. Starting dose for almost half of patients was less than the approved 160-mg dose, but median overall survival (OS) was in the range of estimated OS in phase III clinical trials. Our objective is to investigate treatment patterns in practice, and statistically compare the efficacy of flexible dosing in an observational study with long follow-ups.

METHODS: Targeted Maximum Likelihood Estimation (TMLE) is a doubly robust approach in analyzing observational data, which allows for the application of a suite of models for estimating a parameter of interest. TMLE was used to estimate OS of patients who started on a lower dose vs.160-mg, considering baseline characteristics. Longitudinal TMLE was used accounting for the time-varying adverse events and treatment to estimate OS in a hypothetical case where all patients were treated with lower dose vs. 160-mg. Sequence analysis provided insight on the different patterns of treatments in the real world.

RESULTS: Patients who started on lower dose vs. 160-mg dose regardless of adjustment afterwards had similar incidence rates of death. Analyzing the data longitudinally also showed that the rate of survival among patients who were treated with 160-mg vs. lower doses were not significantly different. Sequence analysis revealed that most patients that started on 160-mg adjusted to lower doses for a longer time in comparison to 160-mg. Among patients started on or shortly adjusted to 160-mg, 293 patients stayed on 160-mg for ~113 days, and 92 of them lasted for ~410 days. While 652 patients started or adjusted to lower dose lasted on lower dose for ~230 days.

CONCLUSIONS: These results show that OS in CORRELATE when patients were on a flexible dose regime is in the range of OS in Clinical Trials.