VEGFR TKIs Associated with Increased Risk of Treatment-Related Mortality

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(ChemotherapyAdvisor) – The VEGFR tyrosine kinase inhibitors (TKIs) pazopanib, sunitinib, and sorafenib were associated with an increased risk of fatal adverse events (FAEs), results of a meta-analysis published in the Journal of Clinical Oncology online February 6 have shown.

Toni K. Choueiri, MD, of Dana-Faber Cancer Institute, Boston, MA, and colleagues reviewed ten randomized, controlled trials identified from MEDLINE and PubMed databases published between January 1966 and February 2011. Sorafenib is approved to treat renal cell cancer (RCC) and hepatocellular cancer; sunitinib, RCC and GI stromal tumor; and pazopanib, RCC.

The meta-analysis included 2,856 patients from sorafenib trials; 1,388 from sunitinib trials, and 435 from pazopanib trials. The investigators found that incidence of FAEs related to VEGFR TKIs was 1.5% vs. 0.7% for control/placebo patients. Risk of developing an FAE was more than two-fold higher with the TKIs (RR 2.23; P=0.023). A subgroup analysis showed no difference in rate of FAEs between the TKIs and tumor types, and there was no evidence of publication bias.

The most frequently occurring FAE was hemorrhage, reported in four trials, followed by myocardial infarction, reported in five trials. Other FAEs included abnormal hepatic function or failure, sepsis, ischemic stroke, pulmonary embolism, dehydration, and sudden death.

“To the best of our knowledge, this is the first meta-analysis to demonstrate a significantly increased risk of death as a result of VEGFR TKI–related FAEs,” they wrote, adding that despite the results, all three drugs should be offered to patients. “However, 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,” they concluded.


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