NEW YORK (Reuters Health) – While treatment of several malignancies with VEGFR (vascular endothelial growth factor receptor) tyrosine kinase inhibitors has improved patient outcomes, the agents are associated with increased risk of treatment-related fatal adverse events.
That’s according to the results of a meta-analysis reported in the Journal of Clinical Oncology published online February 6.
“This is the second meta-analysis to implicate the inhibition of the VEGF pathway with an increased risk of FAEs (fatal adverse events) in patients with cancer,” the authors note. As they point out, the VEGF pathway is critical to several processes such as wound healing, cardiomyocyte homeostasis and neovascularization.
For their study, Dr. Toni K. Choueiri, with the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts, and colleagues identified ten randomized controlled trials of pazopanib, sunitinib or sorafenib involving a total of 4679 patients
Overall, the rate of treatment-related fatal adverse events was 1.5% in the VEGFR TKI arm compared with 0.7% in the control arm, which translated to a relative risk of 2.23 (p=0.023), the investigators found.
While the determination of treatment-related FAEs was likely somewhat subjective, they point out, the rate did not differ by tumor type or the agent being tested.
Nonetheless, Dr. Choueiri and colleagues emphasize that the three drugs improve outcomes of patients with renal cell carcinoma, hepatocellular carcinoma and GI stromal tumor “and should continue to be offered to these patients.”
“However,” they conclude, “as this class of drugs gains greater clinical use, practitioners must be aware of the risks associated with their use and must provide rigorous monitoring to continue to improve patient outcomes.”
