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Updated: May 21, 2026
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Published on: March 20, 2026
Treatment-related mortality with vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy in
Shanthi Sivendran1, Ziyue Liu, Louis J Portas
1Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, NY, United States. shanthisivendran@gmail.com
Background:
Several vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI) are now approved by regulatory agencies and are important in the treatment of solid tumor malignancies. The risk of fatal adverse events (FAEs) with these agents is not well characterized.
Methods:
PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating sunitinib, sorafenib, pazopanib, and vandetanib in patients with all malignancies. Thirteen eligible randomized controlled trials were included in a meta-analysis and the number of FAEs (defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) criteria) was extracted and study quality was calculated. Incidence rates and relative risks were calculated for all thirteen studies as well as for the subset of patients with renal cell carcinoma.
Results:
Analysis of the 5164 patients across 13 RCTs revealed that the relative risk was 1.64 (95% CI, 1.16, 2.32; P=0.01; incidence 2.26% vs. 1.26%) for the association of a VEGFR TKI with FAEs using a random-effects model. All exploratory subgroup analyses indicated a trend toward an increase risk of FAEs with VEGFR TKI treatment, though the subgroup analyses reached statistical significance for renal carcinoma studies, studies utilizing placebo as the control arm, and studies evaluating sorafenib.
Interpretation:
This analysis suggests that VEGFR TKIs are associated with a significant increase in the risk of FAEs in patients with advanced solid tumors.
Insights
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) increase the risk of fatal adverse events (FAEs) in patients with advanced solid tumors. This meta-analysis found a 1.64 relative risk of FAEs with VEGFR TKI treatment.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) are crucial for treating solid tumors.
- The risk of fatal adverse events (FAEs) associated with VEGFR TKIs requires thorough characterization.
Purpose of the Study:
- To evaluate the risk of FAEs in patients treated with VEGFR TKIs.
- To quantify the association between VEGFR TKI therapy and FAEs.
Main Methods:
- A meta-analysis of 13 prospective randomized controlled trials (RCTs) published between 2001 and 2011.
- Included trials evaluated sunitinib, sorafenib, pazopanib, and vandetanib in patients with various malignancies.
- Extracted data on FAEs (defined by CTCAE criteria) and calculated incidence rates and relative risks.
Main Results:
- Analysis of 5164 patients revealed a 1.64 relative risk (95% CI, 1.16-2.32; P=0.01) of FAEs with VEGFR TKI treatment (2.26% vs. 1.26%).
- Subgroup analyses showed a trend towards increased FAE risk with VEGFR TKIs.
- Statistical significance for increased FAE risk was observed in renal cell carcinoma studies, placebo-controlled trials, and studies of sorafenib.
Conclusions:
- VEGFR TKIs are associated with a significant increase in the risk of fatal adverse events in patients with advanced solid tumors.
- These findings highlight the importance of monitoring for FAEs in patients receiving VEGFR TKI therapy.
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