Assessment of pazopanib-related hypertension, cardiac dysfunction and identification of clinical risk factors for their development

BACKGROUND: Antineoplastic therapy with the tyrosine kinase inhibitor pazopanib in patients with advanced/metastatic renal cell carcinoma (mRCC) has been associated with hypertension (HTN), cardiomyopathy, and cardiac dysrhythmias. We therefore assessed the cardiovascular (CV) risk with pazopanib in a clinical setting. METHODS: Medical records of 35 antineoplastic-naïve mRCC patients newly started on pazopanib were retrospectively reviewed at a single academic medical center. Assessment of the hypertensive response and adverse cardiac events associated with pazopanib was the primary objective. Outcomes were defined using the National Cancer Institute’s Common Terminology Criteria for Adverse Events v4.0. Potential clinical risk factors were investigated with univariate and multivariable logistic regression. RESULTS: Pazopanib-induced HTN was observed in 57% of patients. Median maximal systolic blood pressure (SBP) during pazopanib treatment was 167.5 mmHg with median time to event of 24.5 days. New-onset HTN occurred in 6/14 (43%) patients. Baseline SBP > 130 mmHg (odds ratio [OR]: 5.32; 95% confidence interval [CI]: 0.94-29.99; p = 0.058) and ACEi/ARB use (OR: 4.88; 95% CI: 1.05 22.84; p = 0.044) were risk factors for pazopanib-induced HTN. When HTN was excluded, 34% of patients developed a CV adverse event. Age ≥ 60 years (OR: 8.72; 95% CI: 0.74-513.26; p = 0.105) trended towards being a predictor for a non-HTN CV adverse event. CONCLUSIONS: Our findings suggest that pazopanib has a broad CV toxicity profile in treatment-naïve mRCC patients headlined by a rapid and striking hypertensive response. More intensive BP control prior to starting pazopanib and standardization of CV surveillance particularly in older patients may optimize oncologic care while minimizing CV risk.