# Trifluridine/Tipiracil Plus Bevacizumab Versus Regorafenib in Elderly Patients with Refractory Metastatic Colorectal Cancer: A Real-World Comparative Study

## TL;DR

This study found that combining trifluridine/tipiracil with bevacizumab improves survival and reduces side effects in elderly patients with advanced colorectal cancer compared to regorafenib.

## Contribution

The study provides real-world evidence that FTD/TPI plus bevacizumab is more effective and safer for elderly patients with refractory metastatic colorectal cancer.

## Key findings

- FTD/TPI plus bevacizumab significantly improved overall survival compared to regorafenib (12.5 vs. 6.5 months).
- Combination therapy had lower treatment discontinuation rates and fewer severe side effects.
- More patients on the combination therapy received subsequent treatments due to better tolerability.

## Abstract

As society ages, treating elderly patients with advanced colorectal cancer becomes increasingly challenging due to their fragility and intolerance to toxic side effects. This study compared two standard late-line treatments—trifluridine/tipiracil (FTD/TPI) combined with bevacizumab versus regorafenib—specifically in elderly Asian patients. We analyzed real-world data to determine which therapy offers better survival and safety. Our findings suggest that the combination of FTD/TPI plus bevacizumab was associated with significantly longer overall survival (12.5 vs. 6.5 months) compared to regorafenib. Crucially, the combination therapy had milder side effects and significantly lower treatment discontinuation rates, allowing elderly patients to continue therapy and receive subsequent treatments. This study highlights the importance of selecting tolerable treatments to maximize survival outcomes in this vulnerable population.

Background: Taiwan’s transition to a super-aged society presents challenges in managing elderly patients with refractory metastatic colorectal cancer (mCRC). This study evaluated the real-world effectiveness of trifluridine/tipiracil (FTD/TPI) plus bevacizumab versus regorafenib in this specific geriatric population. Methods: A retrospective study analyzed patients aged ≥ 65 treated between 2019 and 2023. Patients received regorafenib (n = 46) or FTD/TPI plus bevacizumab (n = 35). Primary endpoints included overall survival (OS) and time to treatment failure (TTF). Results: FTD/TPI plus bevacizumab was associated with significantly longer median OS compared to regorafenib (12.5 vs. 6.5 months; p = 0.039). In multivariate analysis, the combination regimen was identified as an independent predictor of favorable TTF (adjusted HR 0.44, 95% CI 0.22–0.91, p = 0.028). Regorafenib was associated with symptomatic toxicities like hand–foot skin reaction (58.7%), while the combination primarily caused asymptomatic neutropenia. Crucially, permanent discontinuation due to adverse events was significantly lower in the combination arm (2.9% vs. 30.4%, p < 0.001), facilitating a higher proportion of patients receiving subsequent systemic therapy (45.7% vs. 17.4%, p = 0.011). Conclusions: FTD/TPI plus bevacizumab is associated with improved survival outcomes and better tolerability than regorafenib. By demonstrating a manageable safety profile and minimizing treatment attrition, this regimen ensures a sustainable continuum of care, representing a favorable therapeutic option for elderly patients.