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Neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors

Objective To explore the association of peripheral neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) use in patients with cancer. Methods Published data search up to November 2018 reporting peripheral neuropathy in patients with cancer treated with VEGFR-TKIs was performed. The primary outcome was presence of peripheral neuropathy at the end of the trial. Random-effects meta-analysis was performed to estimate relative risk (RR) of individual treatment. Results Thirty randomized clinical trials (RCTs) including 12,490 patients with cancer were included in this analysis. Eight studies compared VEGFR-TKIs with placebo and the remaining studies compared VEGFR-TKIs with the standard chemotherapeutic regimen. When compared against placebo, VEGFR-TKIs were associated with a higher risk of peripheral neuropathy (RR 1.76; 95% confidence interval [CI] 1.13–2.75, p = 0.01). Similarly, a stronger association was noted for sensory neuropathy with VEGFR-TKIs monotherapy (RR 1.61; 95% CI 1.09–2.37, p = 0.02). Risk of peripheral neuropathy with VEGFR-TKIs was higher even when they were compared against control (either placebo or standard chemotherapeutic agents) (RR 1.08; 95% CI 1.01–1.15, p = 0.03). High-grade neuropathy (RR 1.28; 95% CI 1.06–1.54, p <0.01) and high-grade sensory neuropathy (RR 1.38; 95% CI 1.09–1.74, p < 0.01) were noted more frequently with VEGFR-TKIs treatment compared against control. Conclusions VEGFR-TKIs therapy appeared to be associated with an increased risk of neuropathy.