Trifluridine-tipiracil versus radioembolization for patients with refractory colorectal liver metastases: A real-world data analysis.

Abstract

160 Background: Liver-directed and systemic therapies are available for refractory colorectal liver metastases (CRLM), but comparative survival evidence between selective internal radiation therapy (SIRT) and trifluridine/tipiracil (FTD/TPI) is lacking. Furthermore, the optimal selection of patients who benefit most from SIRT can be improved. Methods: Patients with CRLM treated with SIRT or FTD/TPI (2015-2023) were identified from the Netherlands Cancer Registry. To adjust for baseline imbalances, standardized mortality ratio weighting (SMRW) was applied in the total cohort and stabilized inverse probability of treatment weighting (sIPTW) in the liver-only subgroup. Overall survival (OS) was analyzed using weighted Cox models and adjusted Kaplan–Meier curves. Prespecified subgroups included time from metastatic diagnosis to treatment (<18 vs. ≥18 months), sex, primary tumor location, RAS/BRAF status, prior liver-directed therapy, and number of CRLM. Results: Of 701 patients, 113 received SIRT and 588 received FTD/TPI for refractory disease. Median follow-up was 52.3 months. In the unadjusted cohort, SIRT was associated with longer OS (HR 0.58, [95% CI 0.48-0.72]), with a median OS of 8.9 (95% CI 6.7-10.9) vs. 5.1 months (95% CI 4.6-5.7). After SMRW, this benefit persisted (HR 0.62 [0.48-0.80]), median OS 8.9 (IQR 4.4-16.1) versus 5.6 months (IQR 3.2-9.9); estimated 1-year OS of 36.3% versus 19.4%. In patients with liver-only CRLM (n=138), after sIPTW, the benefit for SIRT versus FTD/TPI was HR 0.48 (95% CI 0.31-0.76), median OS 10.6 (IQR 6.4-16.3) versus 5.8 months (IQR 3.2-10.3); estimated 1-year OS of 42.4% versus 17.0%. The benefit of SIRT was conserved across prespecified subgroups, with particularly favorable outcomes in patients with prior liver-directed therapy. Conclusions: In this population-based study, SIRT was associated with a significant OS benefit compared to FTD/TPI after adjustment of confounders, particularly in patients with liver-only CRLM (sIPTW) and in those with prior liver-directed therapy (SMRW), supporting SIRT as a salvage treatment option in selected patients. Subgroup analyses after adjustment with SMRW. Subgroup HR (99% CI) Median OS SIRT (months) Median OS FTD/TPI(months) Prior liver-directed therapy 0.45 (0.24-0.86) 10.9 7.4 No prior liver-directed therapy 0.75 (0.49-1.16) 8.3 5.1 Right-sided colon 0.65 (0.36-1.18) 6.4 5.7 Left-sided colon 0.61 (0.36-1.06) 12.8 5.9 Rectum 0.48 (0.26-0.88) 9.9 4.3 RAS wildtype 0.60 (0.40-0.89) 12.9 8.4 RAS mutation 0.58 (0.36-0.95) 6.9 4.6 Time from mCRC diagnosis to treatment <18 months 0.60 (0.39-0.93) 8.1 5.5 Time from mCRC diagnosis to treatment ≥18 months 0.62 (0.39-0.97) 12.5 6.9 FTD/TPI, trifluridine-tipiracil; mCRC, metastatic colorectal cancer; SIRT, selective internal radiation therapy; SMRW, standardized mortality ratio weighting.