Case-control trial of association of use of angiogenesis inhibitor with risk of arterial dissection of aneurysm in patients with metastatic colorectal cancer

Pharmacovigilance signals have suggested a potential risk of arterial dissections or aneurysms associated with angiogenesis inhibitors. A nationwide case-control trial in France evaluated the association between exposure to angiogenesis inhibitors (bevacizumab, aflibercept, ramucirumab, and regarofenib) for metastatic colorectal cancer (mCRC) with the occurrence of hospitalization for arterial dissections or aneurysms in clinical practice. The trial included 34.733 patients with a mCRC diagnosis between 2012 and 2017, followed through 2019. A total of 195 incident cases (0.6%) of arterial dissections or aneurysms were observed. These patients were matched 1:10 for age, sex, and time since cohort entry to patients without arterial dissections or aneurysms (n=1950). The median age was 69 (IQR 63-73) years for cases and 68 (62-73) years for controls. A total of 141 cases (72.3%) and 1381 controls (70.8%) were exposed at any timepoint to angiogenesis inhibitors. After adjustment for cardiovascular risk level, no association was observed between exposure and the occurrence of arterial events (OR 1.07; 95% CI 0.75-1.52). No associations were found with either recency or cumulative duration of exposure. The authors conclude that these findings suggest that the established benefits of antiangiogenic drugs in mCRC outweigh the potential risk of arterial dissections an aneurysms.