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Comparative evaluation of cardiovascular risks among nine FDA-approved VEGFR-TKIs in patients with solid tumors: a
Wanting Hou1, Mingfu Ding2, Xiaohua Li3
1Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Sichuan, China.
Purpose:
The present meta-analysis study was performed to identify the potential cardiotoxicity risks when using Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) as anticancer drugs in patients with solid tumors.
Methods:
Pubmed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for the randomized controlled trials. We have included 45 randomized controlled trials (RCTs) associated with nine VEGFR-TKIs Food and Drug Administration (FDA)-approved drugs used to treat patients with solid tumors. To evaluate the trials' risk of bias, Cochrane Risk of Bias Tool was assessed. A direct comparison was assessed by RevMan5.3 software, calculating the odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was tested by the I2 statistic and Chi-square test for P value. Bayesian network meta-analysis was performed using Stata 15.0 and GeMTC 0.14.3 software, calculated OR along with corresponding 95% credible interval (CrI). The model's convergence was evaluated by the potential scale reduced factor (PSRF). Consistency between direct and indirect comparisons was assessed by the "node-splitting" method.
Results:
In this network meta-analysis, a total of 20,027 patients from 45 randomized controlled trials and associated with nine FDA-approved VEGFR-TKIs (axitinib, cabozantinib, lenvatinib, nintedanib, pazopanib, regorafenib, sorafenib, sunitinib, vandetanib), were enrolled. Findings indicated that lenvatinib had the most significant probability of provoking all grades cardiovascular incident and hypertension, followed by vandetanib, cabozantinib, axitinib, pazopanib, sorafenib, sunitinib, regorafenib and nintedanib. The nine agent's severe cardiovascular and severe hypertension risk was probably similar. The ranking probability of cardiac toxicity shows that vandetanib ranked most likely to have the highest risk for cardiotoxicity among all the VEGFR-TKIs reviewed, followed by pazopanib, axitinib, sorafenib, sunitinib. In contrast, regorafenib and nintedanib did not exhibit an increased risk of cardiac damage.
Conclusions:
The association between the nine VEGFR-TKIs with potential cardiotoxicity occurrence was reviewed. Both the regorafenib and nintedanib did not display detectable signs of cardiotoxic damage. In contrast, lenvatinib and vandetanib are ranked to have the most severe cardiotoxicity side impacts. These results may provide information for clinical practice guidelines, implementing strategies in selecting the adequate VEGFR-TKIs, and understanding the cardiovascular toxicity inflicted by the VEGFR-TKIs.
Prospero Identifier:
CRD 42,020,167,307.
Insights
Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) can cause cardiotoxicity. Lenvatinib and vandetanib show the highest risk, while regorafenib and nintedanib appear safe for cardiac health.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) are crucial anticancer agents for solid tumors.
- Assessing the cardiotoxicity of these drugs is vital for patient safety and treatment selection.
Purpose of the Study:
- To systematically evaluate the cardiotoxicity risks associated with nine Food and Drug Administration (FDA)-approved VEGFR-TKIs.
- To compare the relative cardiotoxicity profiles of these agents in patients with solid tumors.
Main Methods:
- A Bayesian network meta-analysis of 45 randomized controlled trials (RCTs) involving 20,027 patients.
- Included nine FDA-approved VEGFR-TKIs: axitinib, cabozantinib, lenvatinib, nintedanib, pazopanib, regorafenib, sorafenib, sunitinib, and vandetanib.
- Assessed risk of bias using the Cochrane Risk of Bias Tool and analyzed data using RevMan5.3 and Stata 15.0.
Main Results:
- Lenvatinib demonstrated the highest probability of causing all grades of cardiovascular events and hypertension.
- Vandetanib ranked highest for severe cardiotoxicity risk, followed by pazopanib, axitinib, sorafenib, and sunitinib.
- Regorafenib and nintedanib showed no increased risk of cardiac damage.
Conclusions:
- Significant variations in cardiotoxicity exist among VEGFR-TKIs.
- Lenvatinib and vandetanib present the most severe cardiotoxicity concerns.
- Regorafenib and nintedanib appear to be safer alternatives regarding cardiovascular side effects, informing clinical decision-making.
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