Drug & Device Development

Tyrosine kinase inhibitors linked to increased treatment-related mortality

Last Updated: 2012-02-14 15:30:02 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Drugs like sorafenib, sunitinib, and pazopanib - i.e., vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors - have improved cancer outcomes, but a new meta-analysis shows they also increase patients' risks for treatment-related fatalities.

"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 researchers note. As they point out, the VEGF pathway is critical to several processes such as wound healing, cardiomyocyte homeostasis, and neovascularization.

For their study, reported online February 6 in the Journal of Clinical Oncology, Dr. Toni K. Choueiri with the Dana-Farber Cancer Institute in Boston, Massachusetts, and colleagues identified ten randomized controlled trials of pazopanib (Votrient), sunitinib (Sutent), or sorafenib (Nexavar) involving a total of 4679 patients

Overall, the rate of treatment-related fatal adverse events was 1.5% in patients receiving VEGFR TKIs, compared with 0.7% in control groups, which translated to a relative risk of 2.23 (p=0.023).

While the determination of treatment-related FAEs was likely somewhat subjective, the rate did not differ by tumor type or the agent being tested, the authors say.

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."

SOURCE: http://bit.ly/zW3xlQ

J Clin Oncol 2012.