Major adverse cardiovascular event risk higher with targeted therapies for kidney cancer
Click Here to Manage Email Alerts
Targeted cancer therapy had a higher association with risk for major adverse cardiovascular events than cytokine therapy among patients with advanced renal cell carcinoma, according to study results.
The findings, published in JACC: CardioOncology, specifically showed higher incidence of myocardial infarction, ischemic stroke and heart failure among patients treated with targeted therapy.
Rationale and methods
The risk for major adverse cardiovascular events associated with targeted therapy among patients with advanced renal cell carcinoma remains unclear, according to study background.
Dong-Yi Chen, MD, researcher in the division of cardiology and department of internal medicine at Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine in Taiwan, and colleagues gathered retrospective data from Taiwan’s National Health Insurance Research Database on 2,785 patients (median age, 63 years; 73.6% men) with advanced renal cell carcinoma who received either targeted therapy (n = 2,257) — sunitinib (Sutent, Pfizer), sorafenib (Nexavar, Bayer), pazopanib (Votrient, Novartis), everolimus or temsirolimus (Torisel, Pfizer) — or cytokine therapy (n = 528) from 2007 to 2018.
They used Cox proportional hazards models and stabilized inverse probability of treatment weighting to estimate the risk for major adverse cardiovascular events, including myocardial infarction, ischemic stroke, heart failure and cardiovascular death.
Key findings
Results showed major adverse cardiovascular event incidence rates of 6.65 per 100 person-years with targeted therapy compared with 3.36 per 100 person-years with cytokine therapy (HR = 1.8; 95% CI, 1.19-2.74).
Researchers identified independent risk factors associated with targeted therapy-associated major adverse cardiovascular events, including baseline history of heart failure (HR = 3.88; 95% CI 2.25-6.71), atrial fibrillation (HR = 3.6; 95% CI, 2.16-5.99), venous thromboembolism (HR = 2.5; 95% CI, 1.27-4.92), ischemic stroke (HR = 1.88; 95% CI, 1.14-3.11) and age of 65 years or older (HR = 1.81; 95% CI, 1.27-2.58).
Of note, researchers found higher risk for major adverse cardiovascular events among patients treated with sorafenib (HR = 1.94; 95% CI, 1.11-3.39) and temsirolimus (HR = 2.11; 95% CI, 1.24-3.59) compared with sunitinib.
Limitations of the study included its retrospective nature and the relatively small sample size in the targeted therapy group, researchers noted.
Implications
“Detailed evaluation of targeted therapy-related adverse events is important in informing the treatment of advanced renal cell carcinoma,” Chen and colleagues wrote. “Identifying high-risk patients and addressing cardiotoxicity early is crucial when treating patients with targeted therapies.”
These findings can be placed in the context of contemporary advanced renal cell carcinoma therapies and how this work influences the field, as the past decade has seen a significant shift from cytokines toward vascular epidermal growth factor receptor TKIs or combination regimens of VEGFR TKIs and checkpoint inhibitors, according to an accompanying editorial by Avirup Guha, MD, MPH, RPVI, FICOS, FACC, inaugural director of cardio-oncology at Medical College of Georgia; Neeraj Agarwal, MD, professor of medicine and a presidential endowed chair of cancer research at Huntsman Cancer Institute; and Nicolas Sayegh, MD, postdoctoral research fellow at Huntsman Cancer Institute.
“To make evidence-based guidelines, a prospective study is necessary, and hypotheses related to the use of a proactive approach compared with the use of a reactive approach could be tested,” they wrote. “This could also inform subsequent clinical trials to justify more intensive cardiovascular monitoring and management. In the meantime, high-quality data as these should be a guide to insurance companies, providers and legislators to keep patients first while approaching the problem at hand.”
References:
- Chen DY, et al. JACC CardioOncol. 2022;doi:10.1016/j.jaccao.2022.05.002.
- Guha A, et al. JACC CardioOncol. 2022;doi:10.1016/j.jaccao.2022.05.007.
Collapse
Click Here to Manage Email Alerts