Julien Taieb ^1* Marwan Fakih ² Gabor Liposits ³ Gerald W Prager ⁴ Eric Van Cutsem ⁵ Fortunato Ciardiello ⁶ Nadia Amellal ⁷ Elizabeth Calleja ⁸ Mei Liu ⁸ Lucas Roby ⁷ Josep Tabernero ⁹ Thierry André ¹⁰

• ¹ Université Paris Cité, Paris, France
• ² City of Hope Comprehensive Cancer Center, Duarte, United States
• ³ Gødstrup Hospital, Herning, Denmark
• ⁴ Department of Medicine I, Medical University Vienna, Vienna, Austria
• ⁵ University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
• ⁶ University of Campania Liuigi Vanvitelli, Naples, Italy
• ⁷ Servier International Research Institute, Suresnes, France
• ⁸ Taiho Oncology, Inc., Princeton, United States
• ⁹ Vall d’Hebron Hospital Campus, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
• ¹⁰ Sorbonne University and Saint-Antoine Hospital, APHP, Paris, France

Background: Trifluridine/ piracil (FTD/TPI) is approved as monotherapy and in combina on with bevacizumab for the treatment of pa ents with refractory metasta c colorectal cancer (mCRC). FTD/TPI plus bevacizumab showed good tolerability in the phase 3 SOLSTICE (first-line) and SUNLIGHT (later-line) trials. This pooled analysis was performed to further characterize the safety of FTD/TPI plus bevacizumab and to compare safety in untreated and previously treated pa ents with mCRC.Methods: Pa ents must have received at least one dose of FTD/TPI plus bevacizumab in SOLSTICE (NCT03869892) or SUNLIGHT (NCT04737187). Treatment-emergent adverse events (TEAEs) in SOLSTICE and SUNLIGHT were graded per Common Terminology Criteria for Adverse Events versions 4.03 and 5.0, respec vely. Times to onset/resolu on of grade ≥3 hematologic TEAEs were assessed using Kaplan-Meier methodology. Treatment-related adverse events (TRAEs) were analyzed by age and Eastern Coopera ve Oncology Group performance status (ECOG PS).The pooled safety popula on comprised 669 pa ents (SOLSTICE, n=423; SUNLIGHT, n=246). Grade ≥3 TEAEs were reported more frequently in SOLSTICE than in SUNLIGHT (86.8% vs. 72.4%), the most common being neutropenia and anemia. Overall, granulocyte colony-s mula ng factor was used in 30.6% of pa ents. Median me to resolu on of grade ≥3 hematologic adverse events/neutropenia to grade ≤2 was 8 days. Grade ≥3 TRAEs were more frequent in pa ents aged ≥75 years and those with an ECOG PS of 0 versus 1 or 2.Conclusions: FTD/TPI plus bevacizumab showed a consistent and manageable safety profile across firstand later-line mCRC treatment, including in vulnerable pa ents. Hematologic TEAEs were mostly reversible with appropriate management.