Background
The TRAVASTIN study dentified plasma Tie2 as the first vascular response biomarker for bevacizumab in metastatic colorectal cancer. Tie2-defined vascular responders had significantly longer progression-free survival (PFS) compared to nonresponders. Here, we report overall survival (OS) in TRAVASTIN after 7.7 years of follow-up, explore efficacy of bevacizumab use and reuse, and assess plasma Tie2 performance as a response biomarker.
Methods
This single-center, prospective study recruited 70 patients with newly diagnosed, large volume, metastatic colorectal cancer. Patients received first-line oxaliplatin-fluoropyrimidine chemotherapy plus bevacizumab. After disease progression, 22 patients were randomized to receive second-line fluorouracil-irinotecan chemotherapy with or without bevacizumab. A vascular response was defined as a 5% or more reduction in plasma Tie2 within 9 weeks of starting treatment. Survival outcomes were estimated using Kaplan-Meier statistics and analyzed using Cox proportional hazards regression.
Results
The updated median PFS and OS were 9.7 months (95% confidence interval [CI] 8.7-11.6) and 19.2 months (95% CI, 16.7-22.0), respectively. Multivariable analysis of key prognostic variables showed Tie2-defined vascular response associated with a significantly improved PFS (hazard ratio [HR] 0.49, 95% CI, 0.29-0.85, P = .011) and moderately improved OS (HR 0.71, 95% CI, 0.42-1.2, P = .195). Patients with a Tie2-defined vascular response to first-line bevacizumab therapy had a 3.7-month longer median OS with bevacizumab reuse than chemotherapy alone (10.5 months vs. 6.8 months, respectively), although this was not statistically significant.
Conclusion
Plasma Tie2 is a response biomarker for PFS benefit with first-line bevacizumab in metastatic colorectal cancer, although OS benefit was not significant in TRAVASTIN. Our study highlights the promising use of Tie2 to guide bevacizumab treatment, including retreatment, in colorectal cancer.
