(ChemotherapyAdvisor) – Vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs) do not appear to be associated with an increased risk of venous thrombotic events (VTEs) in patients with advanced cancers, according to a meta-analysis of data from randomized clinical trials, published online in the journal Critical Reviews in Oncology/Hematology.

However, previously reported meta-analyses have “consistently” supported an association between these agents and a modest increase in the risk of “rare but potentially life-threatening” arterial thrombotic events, regardless of tumor type, the authors cautioned.

The new meta-analysis “corroborates the lack of an association of VEGFR TKIs with VTEs in a range of advanced solid tumors,” reported senior author Toni K. Choueiri, MD, of the Kidney Cancer Center, Dana Farber Cancer Institute, Brigham and Women’s Hospital and Harvard Medical School in Boston, MA, and coauthors.

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“These data are somewhat reassuring and one of the implications of our finding may be that patients with recent but controlled VTE probably should not be denied a VEGFR TKI” treatment, they wrote.

Multitargeted VEGFR TKIs and the VEGF-A inhibitor bevacizumab have been found to be associated with an increased risk of arterial thrombotic events, the authors noted. However, associations with VTEs has been less clear and “controversial,” they noted, and at least one previous meta-analysis failed to identify any increase in VTE risk associated with bevacizumab.

To clarify the relative risks (RRs) of VTEs associated with approved VEGFR TKIs (including sunitinib, sorafenib, pazopanib, vandetanib or axitinib), the authors conducted a systematic review and statistical meta-analysis of data from nine randomized phase 3 clinical trials and eight randomized phase 2 trials, representing a total of 7,441 patients.

The meta-analysis did not include bevacizumab trial data. The authors included data only from randomized trials that compared patient groups treated with or without an approved VEGFR TKI.[VV6] 

“The RR of all grade and high-grade VTE for TKI vs. no TKI was 1.10 (95% CI, 0.73-1.66; P=0.64) and 0.85 (95% CI, 0.58-1.25; P=0.41), respectively,” they reported. “No difference in risk was found based on tumor type, age and trial design.”

“To our knowledge, this meta-analysis represents the largest study addressing the issue of VTEs with VEGFR TKIs,” the authors reported.

The majority of clinical trials included in the analysis “exhibited high quality” and “no heterogeneity or publication bias was found,” they reported, bolstering confidence in the findings. However, the clinical trials included in the analysis “did not enroll patients with significant comorbidities and the regular use of aspirin (>325 mg/day) and anticoagulation were not usually permitted,” the authors noted.

The study was funded by the philanthropic Trust Family Research Fund for Kidney Cancer, the authors reported. Dr. Choueiri disclosed research funding from Bayer/Onyx Pharmaceuticals, Novartis, GSK, Abbot, Genentech, Aveo, and Agennix. Coauthors disclosed financial relationships with Novartis, GSK, Pfizer, Amgen, Celgene, Dendreon, Viatar, BMS, and Aveo.