Efficacy and Safety of Trifluridine–Tipiracil with Vegf Inhibitors and Egfr Inhibitors in Metastatic Unresectable Colorectal Cancer: A Network Meta-Analysis

Document Type

Conference Proceeding

Publication Date

5-27-2026

Publication Title

J Clin Oncol

Keywords

bevacizumab, capecitabine, epidermal growth factor receptor, fluorouracil, folinic acid, irinotecan, oxaliplatin, panitumumab, tipiracil plus trifluridine, vasculotropin inhibitor, adverse drug reaction, aged, colorectal cancer, comorbidity, conference abstract, drug combination, drug comparison, drug dose, drug therapy, drug withdrawal, forest, human, intravenous drug administration, metastasis, monotherapy, multiple cycle treatment, network meta-analysis, neutropenia, overall survival, progression free survival, side effect

Abstract

Background: Introduction:Metastatic unresectable colorectal cancer (mCRC) poses a particular challengewhen patients cannot receive standard first-line FOLFOX (5-fluorouracil, leucovorin, oxaliplatin)or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) because of age, comorbidities, or poorEastern Cooperative Oncology Group (ECOG) performance status. To guide treatment in thisunderstudied population, we conducted a network meta-analysis to indirectly compare theefficacy and safety of alternative regimens, including Trifluridine–tipiracil (TAS‐102), TAS‐102plus bevacizumab, TAS‐102 plus panitumumab, and capecitabine plus bevacizumab in mCRC. Methods: We manually searched major medical databases and identified 12 studies for directand indirect comparisons of alternative agents in mCRC. Forest plots were generated using Rsoftware using random effects model. Results: Progression‐free survival was significantly longer with capecitabine plus bevacizumab(MD 1.97 months; 95% CI 0.39–3.55) and TAS‐102 plus bevacizumab (MD 2.30 months; 95%CI 1.59–3.04) than with TAS‐102 alone, with no meaningful difference between the twocombinations (MD −0.35 months; 95% CI −1.75–1.06). Overall survival improved significantlyonly with TAS‐102 plus bevacizumab versus TAS‐102 monotherapy (MD 2.94 months; 95% CI1.45–4.44), while capecitabine plus bevacizumab and TAS‐102 plus panitumumab did notsignificantly prolong OS (MD 1.54 months; 95% CI −2.02–5.10 and MD 1.50 months; 95% CI−5.22–8.22, respectively). Grade ≥3 neutropenia was much less frequent with capecitabine plusbevacizumab than with TAS‐102 plus bevacizumab (OR 0.02; 95% CI 0.01–0.05) and TAS‐102alone (OR 0.04; 95% CI 0.02–0.10), and occurred less often with TAS‐102 alone than withTAS‐102 plus bevacizumab (OR 0.54; 95% CI 0.40–0.73). TAS‐102 plus bevacizumab achieveda significantly higher disease control rate than TAS‐102 alone (OR 2.55; 95% CI 1.72–3.78), whereas capecitabine plus bevacizumab showed a numerically but not significantly higher DCR(OR 1.99; 95% CI 0.99–4.02), with similar DCR between the two bevacizumab‐based regimens. Conclusions: Capecitabine plus bevacizumab and TAS‐102 plus bevacizumab both improve PFSversus TAS‐102 alone, but only TAS‐102 plus bevacizumab significantly prolongs OS.Capecitabine plus bevacizumab is associated with substantially less grade ≥3 neutropenia, while TAS‐102 plus bevacizumab provides the greatest improvement in disease control.

Volume

44

Issue

16

First Page

e15629

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