Heart-Related Toxicities May Still Occur in AYAs With Kidney Cancer

Young cancer survivors are not immune to the heart-related risks from kidney cancer treatment, recent research showed.

The incidence of heart-related side effects from treatment with VEGF inhibitors were present in adolescents and young adults (AYAs) with for nonmetastatic, high-risk renal cell carcinoma (RCC), a type of kidney cancer, recent study findings demonstrated.

Researchers who conducted the study, which was published in the Journal of National Comprehensive Cancer Network, noted that understanding the risk for cardiovascular disease in AYA cancer survivors is critical to promote heart health in this population.

“These results suggest that younger age and lower comorbidity burden may not reduce the incident risk for cardiovascular toxicities among AYAs receiving VEGF (inhibitor) therapy and suggest a need for further research to understand and mitigate the factors that influence cardiovascular risk in this population, Dr. Wendy Bottinor, assistant professor in the division of cardiology and cardio-oncology at VCU Massey Cancer Center and VCU Health Pauley Heart Center in Richmond, Virginia, said in an interview with CURE®.

Bottinor and colleagues conducted this study to learn more about the growing population of AYA survivors of kidney cancer.

“Over the past decade, the incidence of kidney cancer among AYAs has increased by 3% annually,” she said. “Additionally, five- and 10-year survival are approximately 80%, meaning the majority of AYAs will survive a diagnosis of kidney cancer.”

She noted that it has already been established that the risk for cardiovascular disease is two times greater in AYA cancer survivors compared with people of the same age without a history of cancer. In addition, AYAs with cardiovascular disease have an eight- to 11-times greater risk for death compared with AYAs without cardiovascular disease, according to Bottinor, but despite this knowledge, studies focused on this patient population are sparse.

“AYAs are under-represented in clinical research, so the potential cardiovascular impacts of certain cancer therapies like VEGF (inhibitors) is unclear,” she said. “In pediatric populations, as well as older adults, high blood pressure and cardiac toxicity are common potential effects of VEGF (inhibitors). Whether this was also true for AYAs was previously unknown.”

Researchers analyzed data from 1,572 patients with nonmetastatic, high-risk renal cell carcinoma who were enrolled in a previously conducted trial. These patients were assigned to either Sutent (sunitinib), Nexavar (sorafenib) or placebo.

Several heart-related outcomes were assessed including left ventricular systolic dysfunction (when the left side of the heart has difficulty pumping blood throughout the body) and high blood pressure (greater than 140/90 mm Hg).

Of the patients in the study, 7% were considered AYAs. During a treatment period of 54 weeks, AYAs and non-AYAs had similar rates of left ventricular systolic dysfunction (3% versus 2%, respectively).

“The risk for cardiac toxicity, defined by a decrease in heart pumping function, was similar among AYAs and older adults,” Bottinor said.

In patients assigned placebo, AYAs had lower rates of high blood pressure compared with non-AYAs (18% versus 46%).

For patients assigned Sutent, the incidence of high blood pressure was 29% in AYAs compared with 47% in non-AYAs. In the Nexavar group, 54% of AYAs had high blood pressure compared with 63% in non-AYAs.

“Although the risk for high blood pressure was lower among AYAs, still a third of AYAs receiving (Sutent) and half of AYAs receiving (Nexavar) developed high blood pressure,” Bottinor noted.

Researchers found that AYA status and female sex were each linked with a lower risk for high blood pressure.

“Our findings show that, contrary to what many practitioners would think, AYAs are not protected from the cardiovascular toxicities of VEGFi when compared with an older population,” Bottinor said.

Although determining what preventative measures can be taken for AYAs treated with VEGF inhibitors for renal cell carcinoma requires future investigation, Bottinor noted that there is something patients can do to ensure any indication of heart damage is caught early.

“One thing that can be done in the immediate future is to ensure AYAs are undergoing screening for cardiovascular toxicities and to proactively treat these toxicities (for example, blood pressure medication),” she mentioned.

Bottinor also added that AYAs themselves can also potentially increase the research done in this specific patient population.

“Under-representation of AYAs in research means that there are many unanswered questions,” she said. “We are actively working to find these answers. AYAs, themselves, are our best allies in this endeavor, and we are always looking to partner with AYAs who are interested in research and advocacy.”

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