Plasma Tie2 Predicts Bevacizumab Response in Patients With Metastatic Colorectal Cancer
Key Clinical Takeaways
- Design/Population: The phase 2 TRAVASTIN study was a single-center, prospective trial evaluating bevacizumab-based therapy in 70 patients with newly diagnosed, large-volume metastatic colorectal cancer. Vascular response was defined as a ≥5% reduction in plasma Tie2 within 9 weeks of treatment initiation, with survival outcomes analyzed using Kaplan-Meier and Cox regression methods.
- Key Outcomes: Updated long-term results showed that Tie2-defined responders experienced significantly improved progression-free survival (HR, 0.49; P = .011) and a trend toward improved overall survival. Patients who responded to first-line bevacizumab and were re-treated with bevacizumab in the second line had a longer median overall survival than those treated with chemotherapy alone, although this difference was not statistically significant.
- Clinical Relevance: Plasma Tie2 continues to demonstrate promise as a vascular response biomarker for predicting PFS benefit with bevacizumab in metastatic colorectal cancer. These findings suggest Tie2 may aid in treatment selection and bevacizumab re-treatment strategies, though further validation is needed before clinical implementation.
New long-term data from the TRAVASTIN study reinforce plasma Tie2 as a meaningful vascular response biomarker for bevacizumab among patients with metastatic colorectal cancer (mCRC).
“The TRAVASTIN study identified plasma Tie2 as the first vascular response biomarker for bevacizumab,” stated Rosie Solomon, MD, Manchester University NHS Foundation Trust, Manchester, United Kingdom, and coauthors. In this updated analysis, the investigators further explored the “efficacy of bevacizumab use and reuse and assessed plasma Tie2 performance as a response biomarker.”
In this single-center study, researchers enrolled 70 newly diagnosed patients with large-volume mCRC who received first-line oxaliplatin plus fluoropyrimidine and bevacizumab. Upon disease progression, 22 patients were randomized to receive fluorouracil plus irinotecan with or without bevacizumab. A Tie2-defined vascular response was prespecified as a ≥ 5% reduction in plasma Tie2 levels within 9 weeks of treatment initiation. Primary end points included progression-free survival (PFS) and overall survival (OS).
At analysis, median PFS was 9.7 months and median OS was 19.2 months. Multivariable analysis showed that Tie2-defined vascular response was associated with significantly improved PFS (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29 to 0.85; P = .011) and a nonsignificant trend toward improved OS (HR, 0.71; 95% CI, 0.42 to 1.20; P = .195). Among patients who demonstrated a Tie2-defined vascular response to first-line bevacizumab, median OS was 10.5 months with bevacizumab and 6.8 months with chemotherapy, although this difference was not statistically significant.
“A reduction in plasma Tie2 concentration identified patients with significantly longer progression-free survival, but not overall survival,” concluded Dr Solomon et al. “Tie2-defined vascular responders also derived the greatest benefit from bevacizumab reuse, supporting the potential role of plasma Tie2 monitoring as a response biomarker in metastatic colorectal cancer.”
Source:
Solomon R, Morgan RD, Horsley L, et al. Overall survival for bevacizumab therapy in metastatic colorectal cancer: an updated analysis of the TRAVASTIN study. Clin Colorectal Cancer. Published online: November 12, 2025. doi: 10.1016/j.clcc.2025.11.001
