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P102: Risk Assessment of Arterial Aneurysms and Dissections in Cancer Patients Treated with Oral VEGFR-TKIs using Real-World Data

Poster Presenter

Bora Yeon

Statistician
Korea Institute of Drug Safety and Risk Management
Korea, Republic of

Objectives

This study aimed to evaluate the risk of arterial aneurysms and dissections in cancer patients treated with oral tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR-TKIs) compared with capecitabine as an active comparator.

Method

We conducted a retrospective cohort study using the National Health Insurance Service DB between 2010-2020 in Korea. Patients =40 years who were prescribed oral VEGFR-TKIs or capecitabine were included. Statistical analysis was performed using the Cox model after 1:1 propensity score (PS) matching.

Results

A total of 140,632 patients aged 40 years and older who were prescribed VEGFR-TKIs or capecitabine between January 2010 and December 2020 were screened. Patients with a history of arterial aneurysms and dissections and congenital disease before the index date, as well as those prescribed VEGF inhibitors not for solid tumors between 3 years before the index date and the observational period, were excluded. Therefore, the study included 37,308 patients prescribed VEGFR-TKIs and 90,402 patients prescribed capecitabine. After 1:1 PS matching, a total of 27,535 patients prescribed VEGFR-TKIs were matched with patients prescribed capecitabine. The incidence of arterial aneurysms and dissections within 1 year of treatment initiation was found to be 6.0 per 1,000 person-years (PY) in patients with VEGFR-TKIs and 4.1 per 1,000 PY in patients with capecitabine. The patients with VEGFR-TKIs had a significantly higher risk of arterial aneurysms and dissections than those with capecitabine (HR 1.48, 95% CI 1.08-2.02). The median time for arterial aneurysms and dissections to occur after VEGFR-TKIs use was 114 days (IQR 67-257). In subgroup analysis, a statistically significant risk between the VEGFR-TKIs user and the capecitabine user was observed in female patients (HR 2.08, 95% CI 1.26-3.42), patients aged 65 or older (HR 1.42, 95% CI 1.01-1.99), and patients with a history of dyslipidemia (HR 1.58, 95% CI 1.11-2.24). However, there was no significant difference between VEGFR-TKIs user and capecitabine user with a history of hypertension or diabetes. Sensitivity analysis was performed by changing the follow-up period to 3, 6, or 9 months, which showed a similar trend to the main result. Consistent with the findings of the main analysis, the trend in arterial aneurysms and dissections risk remained unchanged in the as-treated analysis (HR 2.17, 95% CI 1.09-4.29). Furthermore, no statistical association was found when appendicitis was analyzed as a negative control.

Conclusion

The aim of the present research was to evaluate the risk of arterial aneurysms and dissections in patients with oral VEGFR-TKIs within one year from the start of treatment. To the best of our knowledge, this is the first study to confirm the incidence and risk of arterial aneurysms and dissections caused by VEGFR-TKIs using real-world data. The study found that the VEGFR-TKIs users in people aged 40 or older had a 1.48 times higher risk of arterial aneurysms and dissections than capecitabine users, and the incidence rate in the VEGFR-TKIs users was 6.0 per 1,000 PY. The analysis of the as-treated also revealed that the risk of arterial aneurysms and dissections was 2.17 times higher in VEGFR-TKIs users than in capecitabine users. This finding establishes the robustness and reliability of the study result. Additionally, the median time to the occurrence of arterial aneurysms and dissections after VEGFR-TKIs use was 114 days, and arterial aneurysms and dissections could occur throughout the year after VEGFR-TKIs initiation. Therefore, the occurrence of symptoms such as headaches and abdominal pain during the use of VEGFR-TKIs should be considered as potential indicators of arterial aneurysms and dissections, especially in high-risk patients including the elderly, females, and those with dyslipidemia. By being aware of the potential risk of arterial aneurysms associated with VEGFR-TKIs use and detecting them early through screening before complications such as ruptures occur not only can treatment efficacy be increased, but also social and economic losses can be reduced. We are hoped that the results of this study will be provide insights to clinicians who treat cancer patients, contributing to the establishment of a safer drug use environment.