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VEGFR-TKIs significantly increase risk for hand-foot skin reactions

The use of vascular endothelial growth factor receptor tyrosine kinase inhibitors significantly increased the risk for developing all-grade and high-grade hand-foot skin reactions, according to a meta-analysis in the Journal of the American Academy of Dermatology.

The randomized, controlled phase 2 and phase 3 trials included patients with cancer assigned to treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) or control treatments and who had safety data available for hand-foot skin reactions (HFSR).

The meta-analysis, by Fengxia Ding, MD, from the department of pediatric respiratory medicine at the Children’s Hospital of Chongqing Medical University, China, and colleagues, included 24,956 patients from 57 trials.

Overall, 3,536 patients experienced all-grade HFSR. The highest incidence of all-grade HFSR occurred in a phase 2 trial for breast cancer (90.2%; 95% CI, 83.3% to 94.4%), and the lowest incidence occurred in a phase 2 trial for cervical cancer (1.4%; 95% CI, 0.2% to 7.3%).

A total of 1,595 patients experienced high-grade HFSR. The highest incidence was found in a phase 2 trial for breast cancer (66.1%; 95% CI, 56.9% to 74.2%). The lowest incidence was identified in three trials that reported no cases of high-grade HFSR: one phase 2 trial for breast cancer, one phase 2 trial for renal cell carcinoma and one phase 2 trial for cervical cancer.

The use of VEGFR-TKIs significantly increased the risk for developing all-grade HFSR. In a random-effects model, researchers achieved a relative risk of 5.09 (95% CI, 3.52 to 7.35). Furthermore, they found VEGFR-TKIs significantly increased the risk for high-grade HFSR (9.42, 95% CI, 5.59 to 15.90).

Patients with thyroid cancer showed the highest relative risk of all-grade HFSR (12.62; 95% CI, 3.57 to 44.60) and high-grade HFSR (52.90, 95% CI, 7.81 to 358.27).

Moreover, the risk for all-grade and high-grade HFSR adverse events varied significantly by tumor type.

The highest risk for all-grade HFSR was found in patients who received cabozantinib (12.10; 95% CI, 3.01 to 48.54). In high-grade HFSR, researchers identified the highest risk in those who received regorafenib (36.89; 95% CI, 7.41 to 183.72).

Ding and colleagues said that VEGFR-TKI use significantly increases the incidence of HFSR and also varies according to tumor type, the type of VEGFR-TKI used, phase of trials and concomitant usage of anticancer agents. – by Abigail Sutton

Disclosures: The authors report no relevant financial disclosures.