Risk factor analysis for regorafenib-induced severe hypertension in metastatic colorectal cancer treatment

Regorafenib, a multikinase inhibitor, is effective in treating metastatic colorectal cancer (mCRC). Hypertension is a frequently occurring adverse effect caused by regorafenib regardless of previous treatment with vascular endothelial growth factor (VEGF) inhibitors in almost all patients. We identified the risk factors associated with regorafenib-induced severe hypertension. Patients with mCRC (n = 100) who received regorafenib were evaluated retrospectively. The primary endpoint was the evaluation of the risk factors for grade >= 3 hypertension. The association between pre-existing hypertension at baseline and grade >= 3 hypertension symptoms was also assessed. Patients with pre-existing hypertension at baseline accounted for 55% of the total patients. The starting doses of regorafenib were 160 mg (49.0% of patients), 120 mg (29.0%), and 80 mg (22.0%). The incidence of grade >= 3 hypertension was 30.0%. The median time to grade >= 3 symptom development was 7 days (range: 1-56 days). Additional antihypertensive treatment was administered to 83.6% of patients who developed hypertension. Logistic regression analyses revealed that baseline pre-existing hypertension complications and previous anti-VEGF treatment for >= 700 days were independent risk factors for grade >= 3 hypertension development. Further analyses revealed that pre-existing hypertension before anti-VEGF treatment (primary hypertension) was significantly related to the symptom development (adjusted odds ratio, 8.74; 95% confidence interval, 2.86-26.72; P = 0.0001). Our study suggests that pre-existing primary hypertension and previous anti-VEGF treatment for >= 700 days are independent risk factors for regorafenib-induced severe hypertension. Deeper understanding of the symptom nature and management can significantly contribute to safer interventions, necessitating further studies.

Automated summary

The study found that regorafenib treatment can cause hypertension and identified the risk factors associated with severe hypertension. Pre-existing primary hypertension and previous anti-VEGF treatment for >= 700 days were found to be independent risk factors for the development of hypertension.