A Real-World Comparison of Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer in the United States

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Christopher Nevala-Plagemann Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah

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Shashank Sama Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah

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Jian Ying Department of Population Health Sciences, University of Utah, Salt Lake City, Utah

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Jincheng Shen Department of Population Health Sciences, University of Utah, Salt Lake City, Utah

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Benjamin Haaland Department of Population Health Sciences, University of Utah, Salt Lake City, Utah

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Vaia Florou Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah

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Ignacio Garrido-Laguna Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah

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Background: Trifluridine/Tipiracil (TAS-102) and regorafenib are FDA-approved in the United States for treatment of refractory metastatic colorectal cancer (mCRC). FDA approvals of these agents were based on modest improvements in overall survival (OS) compared with best supportive care + placebo in the RECOURSE and CORRECT trials, respectively. This study compared real-world clinical outcomes with the use of these agents. Methods: A nationwide deidentified electronic health record–derived database was reviewed for patients diagnosed with mCRC between 2015 and 2020. Patients who received at least 2 lines of standard systemic therapy followed by treatment with either TAS-102 or regorafenib were included for analysis. Kaplan-Meier and propensity score–weighted proportional hazards models were used to compare survival outcomes between groups. Results: The records of 22,078 patients with mCRC were reviewed. Of these, 1,937 patients received at least 2 lines of standard therapy followed by regorafenib and/or TAS-102. Median OS for the TAS-102 alone or prior regorafenib group (n=1,016) was 6.66 months (95% CI, 6.16–7.18 months) compared with 6.30 months (95% CI, 5.80–6.79 months) for regorafenib alone or prior to TAS-102 (n=921; P=.36). A propensity score–weighted analysis controlling for potential confounders did not demonstrate a significant difference in survival between groups (hazard ratio, 0.99; 95% CI, 0.90–1.09; P=.82). A subgroup analysis did not identify any significant differences in outcomes regarding age, performance status, tumor sidedness, microsatellite instability status, or RAS/RAF status. Conclusions: This analysis of real-world data found that OS was similar for patients with mCRC who were treated with TAS-102 compared with regorafenib. Median OS with both agents in a real-world setting was similar to that shown in the clinical trials that led to their approvals. A prospective trial comparing TAS-102 and regorafenib would unlikely change current management of patients with refractory mCRC.

Submitted July 17, 2022; final revision received September 28, 2022; accepted for publication September 28, 2022. Published online February 22, 2023.

Author contributions: Study concept and design: Nevala-Plagemann, Sama, Garrido-Laguna. Data analysis and interpretation: All authors. Manuscript preparation: All authors.

Disclosures: Dr. Haaland has disclosed serving as a consultant for the National Kidney Foundation, Proxima Clinical Research, Value Analytics Labs, and Guidepoint Global. The remaining authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was support by the Foundation for the National Institutes of Health under award number P30CA042014.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Christopher Nevala-Plagemann, MD, MSCI, Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Room 2143, Salt Lake City, UT 84112. Email: chris.nevala-plagemann@hci.utah.edu
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