Managing adverse events in patients with metastatic colorectal cancer receiving trifluridine/tipiracil in combination with bevacizumab

For patients with metastatic colorectal cancer (mCRC) that is refractory to standard chemotherapy, a recommended standard-of-care treatment in the third-line setting is trifluridine/tipiracil (FTD/TPI) alone or in combination with bevacizumab; other treatment options include fruquintinib or regorafenib. The safety profiles of FTD/TPI and bevacizumab as individual agents are well characterized. Common adverse events (AEs) associated with FTD/TPI include neutropenia, anemia, nausea, and diarrhea, and AEs frequently observed with bevacizumab include hypertension, proteinuria, hemorrhage, venous thromboembolism, and gastrointestinal perforation. Approval of the combination of FTD/TPI plus bevacizumab for the treatment of patients with refractory mCRC in the United States and Europe was based on results from the phase III SUNLIGHT trial. There is clinical value in developing a specific set of recommendations for the prevention or management of the key AEs associated with the combination regimen to inform clinical care and improve patient benefit. In this review, we summarize the safety profile of combination treatment with FTD/TPI plus bevacizumab in patients with refractory mCRC who were enrolled in the SUNLIGHT trial, with a focus on the key AEs of neutropenia, anemia, nausea or vomiting, diarrhea, fatigue, hypertension, and hemorrhage. In addition, we provide recommendations for the management or prevention of these key AEs in clinical practice, based on published literature and expert opinions on effective strategies.