VEGFR-TKIs Associated With Aneurysm, Artery Dissection – Renal and Urology News

Tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR-TKIs) are associated with an increased likelihood of aneurysm and artery dissection, according to recent research.

In a case-control study of 8659 patients with kidney, hepatic, gastrointestinal, or pancreatic cancer from Taiwan’s 2011-2019 National Health Insurance Research Database and the Taiwan Cancer Registry, 1461 patients had aortic aneurysm or dissection and 7198 did not.

Patients treated with sorafenib, sunitinib, or pazopanib had significant 2.0-fold increased odds of an aortic aneurysm or dissection compared with patients not treated with VEGFR-TKIs in adjusted analyses, Chi-Chuan Wang, PhD, of National Taiwan University in Taipei, Taiwan, and colleagues reported in JAMA Network Open. In subgroup analyses, results remained significant only for aortic dissection: VEGF-TKI use was significantly associated with 3.1-fold increased odds of aortic dissection.

Both duration and dose of VEGFR-TKIs appeared to affect risk. Drug exposure for 68 days or more carried 2.6-fold increased odds of the composite of aortic aneurysm and dissection after adjustment, the investigators reported. A total of 61 defined daily doses was significantly associated with 2.7-fold increased odds of the composite outcome. The investigators could not adjust for blood pressure, body mass index, and family history, which are study limitations.

VEGF pathway inhibition may lead to endothelial dysfunction or affect the integrity of the vessel wall, the investigators suggested.

“Health care professionals should closely monitor patients undergoing [VEGFR-TKI] therapy for the development of [aortic aneurysm and aortic dissection],” Dr Wang’s team wrote.

These findings support results from a recent Korean cohort study using national claims data. Among 127,710 patients with various cancer types, 37,308 patients were treated with VEGFR-TKIs (sorafenib, regorafenib, vandetanib, sunitinib, lenvatinib, axitinib, or pazopanib), whereas 90,402 patients received capecitabine chemotherapy. After propensity-score matching 27,535 patients in each group, the risk for aneurysm and artery dissection within 1 year was a significant 1.5-fold higher among patients taking VEGFR-TKIs vs capecitabine, Yun Mi Yu, PhD, of Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University in Incheon, South Korea, and colleagues reported in JAMA Network Open. The incidence rate was 6.0 per 1000 person-years in the VEGFR-TKIs group, and was highest during the first 3 months of treatment. The median time to the onset of aneurysm and artery dissection after VEGFR-TKI prescription was 114 days.

“This suggests that [aneurysm and artery dissection] may occur continuously regardless of the time of drug administration, Dr Yu stated. “Therefore, clinicians should consider the possibility of [aneurysm and artery dissection] incidence after the occurrence of symptoms, such as headache or abdominal pain, at any time after VEGFR-TKI administration.”

Results were similar in women despite estrogen “protection,” older adults, and patients with dyslipidemia.

The FDA is currently evaluating whether regulatory action is required for VEGF inhibitors with respect to aortic aneurysm and dissection.

References:

Wu CW, Huang HY, Lin SY, Wang CC, Huang CF, Wu IH. Vascular endothelial growth factor inhibitors and the risk of aortic aneurysm and aortic dissection. JAMA Netw Open. Published online March 4, 2024. doi:10.1001/jamanetworkopen.2024.0940

Kang S, Yeon B, Kim MS, Yoo M, Kim B, Yu YM. Aneurysm and artery dissection after oral VEGFR-TKI use in adults with cancer. JAMA Netw Open. Published online November 1, 2023. doi:10.1001/jamanetworkopen.2023.45977