Safety and Efficacy of Prophylactic Topical Steroid Administration for Enfortumab Vedotin-related Cutaneous Toxicity

Enfortumab vedotin (EV) is used to treat unresectable/metastatic urothelial carcinoma but often causes cutaneous toxicity (EVRCT) because of Nectin4 expression in the skin, which reduces patients' quality of life and can lead to dose adjustments or discontinuation. We explored whether applying topical steroids prophylactically to intertriginous areas could prevent EVRCT. Five patients received clobetasol propionate on one side and Vaseline on the other. Three patients developed grade >= 2 EVRCT at Vaseline-treated sites, but no EVRCT at clobetasol-treated sites. The results suggest that prophylactic topical steroid application can reduce the incidence of EVRCT, which prompted early study termination and progression to the next trial phase. Patient summary A drug called enfortumab vedotin (EV) used to treat advanced cancer of the urinary tract can cause severe skin reactions. We compared application of a steroid cream or Vaseline to the skin in five patients who were starting EV therapy. Three patients had an EV reaction on Vaseline-treated skin patches but not on steroid-treated skin patches. Because of these positive results, we are testing steroid cream at the start of EV treatment in a larger study.