Prospective observational study investigating the impact of treatment sequence using regorafenib and FTD/TPI for metastatic colorectal cancer on overall survival (OSERO study).

Abstract

103 Background: Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) with or without bevacizumab (BEV) are widely used as a later-line treatment for patients (pts) with metastatic colorectal cancer (mCRC). It is still unclear which is the preferable treatment strategy to start with, either REG, FTD/TPI, or FTD/TPI + BEV in clinical practice. Methods: We conducted a non–intervention, prospective, observational study in pts with mCRC at 41 sites. The key eligibility criteria were ECOG performance status (PS) 0 or 1, pts refractory to or intolerant of fluoropyrimidine, oxaliplatin, irinotecan, anti–angiogenesis, and anti–EGFR therapy if RAS status were wild type, and pts who plan to receive sequential treatment with REG and FTD/TPI BEV. Pts who starts with REG are enrolled in cohort A, FTD/TPI in cohort B, or FTD/TPI plus BEV in cohort C. The primary endpoint is overall survival (OS) of each group. Results: Between September 2020 and December 2022, a total of 501 pts were enrolled and 455 were identified as full analysis set. Pts’ characteristics of cohort A (149 pts) / B (80 pts) /C (226 pts) were as follows: median age 64.0 / 65.5 / 67.0 years, male 53.0 / 52.5 / 55.3%, ECOG PS 0 52.3 / 31.3 / 48.7%, tumor location right–sided 33.6 / 27.5 / 20.4%, RAS wild type 35.6 / 41.3 / 43.4%, and BRAF V600E mutant type 6.7 / 7.5 / 4.0 %. Pts who received subsequent with FTD/TPI BEV in cohort A / REG in cohort B / REG in cohort C were 62.4 / 37.5 / 62.8%. The median OS of cohort A / B / C was 11.8 / 7.1 / 10.2 months. Cox hazard model revealed hazard ratio (HR) 1.40 (95% confidence interval [CI] 1.01–1.94; p = 0.043) for cohort B, and HR 1.04 (95% CI 0.80–1.34; p = 0.784) for cohort C compared with cohort A. After adjusting age, ECOG PS, tumor location, the number of metastatic sites, the adjusted HR were 1.29 (95% confidence interval [CI] 0.87–1.91; p = 0.213) for cohort B, and 1.00 (95% CI 0.75–1.34; p = 0.998) for cohort C compared with cohort A. Conclusions: This study demonstrates that the OS are comparable regardless of whether REG, FTD/TPI, or FTD/TPI + BEV is administered first. Clinical trial information: UMIN000040586 .