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Combining TAS-102 with bevacizumab improves outcomes but may increase adverse events. We conducted a real-world, retrospective, exploratory comparison of two dosing schedules (bi-weekly vs. four-weekly) to describe efficacy, safety, and potential molecular and clinical correlates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed patients with mCRC who were treated with TAS-102 in combination with bevacizumab as late-line therapy from January 2020 to February 2023. Regimen assignment followed physician-patient shared decision-making based on clinical factors and local practice changes after emerging evidence, not randomization. Endpoints included progression-free survival (PFS), overall survival (OS), adverse events (AEs). Analyses were exploratory and hypothesis-generating, with multivariable Cox models for selected covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 92 patients were enrolled in this study. Median PFS was 3.2 months (bi-weekly) vs. 3.7 months (four-weekly), and median OS was 10.0 vs. 9.3 months, with no statistically significant differences. KRAS mutation was associated with inferior OS (7.7 vs. 11.8 months;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.018), whereas TP53 was not. Eastern Cooperative Oncology Group performance status (ECOG-PS)\u2009=\u20092 independently predicted shorter PFS and OS; prior bevacizumab exposure correlated with shorter PFS but not OS. Common adverse events in patients were neutropenia (63.0%), leukopenia (67.0%), anemia (44.6%), malaise (55.4%), nausea (45.7%), anorexia (31.5%), and diarrhea (23.9%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this retrospective, real-world study, the two regimens demonstrated comparable disease control, and the bi-weekly regimen appeared to be better tolerated, representing a reasonable potential alternative. Nevertheless, these findings should be interpreted as exploratory, and future prospective studies are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12672-026-04459-6","type":"journal-article","created":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T07:55:51Z","timestamp":1769932551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A real-world study of Trifluridine\/Tipiracil (TAS-102) combined with bevacizumab as the late-line treatment of metastatic colorectal cancer"],"prefix":"10.1007","volume":"17","author":[{"given":"Shaocheng","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangying","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunye","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiwen","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"issue":"3","key":"4459_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, et al. 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