Antiangiogenic Agents for Cancer May Boost Aneurysm Risk

NEW YORK (Reuters Health) – Caution may be required when using anticancer drugs targeting angiogenesis because of the potential risk of artery dissections or aneurysms, according to researchers in France.

“Given the associated mortality and morbidity of artery dissections or aneurysms and the increasing use of angiogenesis inhibitors in cancer treatment, our findings, based on pharmacovigilance data, deserve to be communicated to the medical oncology community before confirmation and quantification of this risk through population-based epidemiological studies,” Dr. Pernelle Noize of the University of Bordeaux told Reuters Health by email.

Antiangiogenic cancer drugs block vascular endothelial growth factor (VEGF) directly or indirectly via a variety of mechanisms, Dr. Noize and her colleagues note in JAMA Oncology. However, there is little information on potential arterial-wall injuries.

To investigate, the team consulted VigiBase, the World Health Organization’s centralized database of suspected adverse drug reactions. They identified more than 217,000 cases of dissections or aneurysms occurring in all arteries which were potentially associated with the use of 14 antiangiogenic drugs.

Between 2005 and 2019, 494 patients (median age, 67 years) had artery dissections or aneurysms. Most of these cases (88%) were serious, 18% were life-threatening and 120 cases (24%) were fatal.

Bevacizumab was implicated in 222 cases, sunitinib in 71 cases and everolimus in 55. However, 138 patients (28%) were receiving other drugs in addition to antiangiogenics that may have been associated with artery dissections or aneurysms.

Overall, hypertension was reported in 51 adverse drug reaction cases, but in only two of 57 cases (3.5%) that involved use of mammalian target of rapamycin inhibitors.

Altogether, say the researchers, signals of disproportionate reporting of artery dissections or aneurysms were found among all antiangiogenic drugs and among nine specific antiangiogenic drugs including everolimus, sunitinib and bevacizumab.

The researchers stress that population-based studies are needed to confirm and quantify the potential risk of artery dissections or aneurysms associated with the receipt of these agents.

SOURCE: JAMA Oncology, online March 18, 2021.

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