Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied.
In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation.
Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant "on-treatment" hypertension was not associated with MACE.
These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI-related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.
Journal of the National Comprehensive Cancer Network : JNCCN. 2023 Oct [Epub]
Vivek Narayan, Tao Liu, Yunjie Song, Joshua Mitchell, JoRean Sicks, Ilana Gareen, Lova Sun, Srinivas Denduluri, Ciaran Fisher, Jesse Manikowski, Mark Wojtowicz, Joseph Vadakara, Naomi Haas, Kenneth B Margulies, Bonnie Ky
1Division of Hematology/Medical Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., 3Center for Statistical Sciences, Department of Biostatistics, Brown University School of Public Health, Providence, Rhode Island., 4Cardiovascular Division, Cardio-Oncology Center of Excellence, Washington University in St. Louis, St. Louis, Missouri., 5Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., 6Geisinger Cancer Institute, Geisinger Medical Center, Danville, Pennsylvania., 2Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.