Efficacy and safety of trifluridine–tipiracil with VEGF inhibitors and EGFR inhibitors in metastatic unresectable colorectal cancer: A network meta-analysis.

e15629 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.