Oral VEGFR TKIs Almost Tripled Risk for Stroke in Older RCC Patients

October 13, 2015

Older patients taking the oral TKIs sorafenib and sunitinib for RCC had a significantly increased risk for cardiovascular events, particularly stroke.

Older patients taking the oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib for renal cell carcinoma (RCC) had a significantly increased risk for cardiovascular events, particularly stroke, according to the results of a study published recently in Cancer.

The analysis used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and found that patients aged 66 or older who received sunitinib or sorafenib had a slightly increased risk for all cardiovascular events, and an almost threefold increased risk for stroke.

“Clinicians should be aware of this adverse effect to prevent or detect its development, provide early interventions, and balance the therapeutic benefit with adverse events,” wrote researchers led by Sekwon Jang, MD, of Inova Comprehensive Cancer and Research Institute in Fairfax, Virginia, who undertook this population-based cohort study to estimate the incidence and relative risk of cardiovascular events related to the use of sunitinib and sorafenib in patients with advanced RCC in a community oncology practice.

The study included SEER data from 670 patients diagnosed with RCC between 2000 and 2009. Sunitinib and sorafenib were administered sequentially in 111 patients; 396 received sunitinib only and 163 received sorafenib only. Overall, 171 of the patients who received both agents had a cardiovascular event, for an overall incidence rate of 1.02 per 1,000 person-days.

Among patients who received one of the two drugs, the incidence rate for coronary heart failure/cardiomyopathy was 0.87 per 1,000 person-days; for acute myocardial infarction, 0.14 per 1,000 person-days; and stroke, 0.14 per 1,000 person-days.

After adjusting for age at diagnosis, sex, comorbidities, and use of other systemic therapy, the use of these oral VEGFR TKIs was associated with a 38% increased risk for cardiovascular events (hazard ratio [HR], 1.38 [95% confidence interval (CI), 1.02–1.87]) as compared with 788 patients diagnosed with advanced RCC between 2007 and 2009 who were eligible for Medicare Part D but did not receive these drugs.

Specifically, patients receiving both of these drugs had a significantly increased risk for stroke (HR, 2.84 [95% CI, 1.52–5.31]). This risk was elevated among those patients who received sorafenib only (HR, 5.30 [95% CI, 1.80–15.61]) and sunitinib only (HR, 2.28 [95% CI, 1.00–5.22]).

“We then examined whether other factors contributed to the elevated risk of stroke,” the researchers wrote. “We found that increasing age and greater comorbidity were also significantly associated with an increased risk of stroke among recipients of either sunitinib or sorafenib.”

Jang and colleagues acknowledged certain limitations with their study, including the possible overestimation of coronary heart failure due to the use of Medicare data, and the reasons why comparator patients did not receive sunitinib or sorafenib or if they received those drugs with supplementary insurance.

Despite the increased risks found in this study, the researchers acknowledged that the overall absolute risk for cardiovascular events was still very low.