VEGFR-TKIs DO NOT CAUSE VT

NEW YORK (Reuters Health) Jan 01 - Treating cancer patients with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) does not appear to increase their risk of venous thromboembolism, researchers from China report.

VEGFR-TKIs have been tied to venous and arterial thromboembolisms, but the small numbers of patients in previous trials have limited the ability to define the actual risk of such events.

In the new study, Dr. Yang Yao and colleagues from Sixth People's Hospital at Shanghai Jiao Tong University did a meta-analysis of 14 prospective clinical trials (6 phase III, 8 phase II) involving 4,430 cancer patients.

The incidence of VTE associated with VEGFR-TKI treatment was 3% (5.5% for sorafenib, 0.5% for sunitinib, 2.2% for vandetanib, and 4.7% for pazopanib), according to the report, which was published online December 6 in the International Journal of Cancer.

After adjusting for confounders, the risk for VTE in these patients did not differ significantly from that of cancer patients not treated with VEGFR-TKIs (relative risk, 0.912; p=0.643). Subgroup analyses of individual VEGFR-TKI drugs produced similar results.

"These data are reassuring and suggest similar to bevacizumab, VEGFR-TKIs do not significantly elevate the risk of VTE, unlike the increase in risk with chemotherapy, especially cisplatin," Dr. Toni Choueiri from Harvard Medical School in Boston and Dr. Guru Sonpavde from the University of Alabama at Birmingham Comprehensive Cancer Center told Reuters Health by email.

"A controlled recent VTE probably should not dissuade the institution of VEGFR-TKI if necessary for optimal therapy," they said. But they cautioned that the trials in the meta-analysis had generally excluded patients with cardiovascular events and thrombotic events within 6 to 12 months.

"Hence, the risk of VTE in those with recent thrombotic events is unknown and judgment is necessary when initiating a VEGFR-TKI in such patients," Dr. Choueiri and Dr. Sonpavde noted.

In a single comparison of lung cancers, there was no significant difference in the incidence or relative risk of VTE in patients with non-small-cell lung cancer (NSCLC) or non-NSCLC, according to the Chinese researchers.

"The current analysis suggests that the use of VEGFR-TKIs does not significantly increase the risk of VTE, and the risk of VTE is driven predominantly by tumor types, host factors, and concomitant usage of anticancer agents," they conclude.

Despite the reassuring findings, physicians and patients still need to consider the risk for thrombotic events, Dr. Alok Khorana from the University of Rochester in New York told Reuters Health by email.

"In general, cancer patients on systemic therapy continue to be at risk for VTE," Dr. Khorana said. He added that, "Other meta-analyses have shown that arterial (as opposed to venous) events continue to be prevalent, so clinicians should remain cognizant of the risk of thrombotic events and educate patients about warning signs and symptoms."

Dr. Shenhong Wu from Stony Brook University School of Medicine in New York cautioned that the new analysis is "limited by small sample size and missing data in many trials with VEGFR-TKIs."

"Further studies are needed to understand the risk of VTE among different VEGFR-TKIs," Dr. Wu told Reuters Health by email.

SOURCE: http://bit.ly/12TnVSg

Int J Cancer 2012.