opathologic and Immunohistochemical Characterization ash to Human Epidermal Growth Factor Receptor

Downloa pose: Human epidermal growth factor receptor (HER) 1 and HER 1/2 inhibitors have shown it against a wide range of solid tumors. However, their use is associated with rash in 40% to f patients, which impacts quality of life and interrupts antineoplastic therapy. The pathologic chartics of affected skin remain unclear, precluding development of rational therapies. The aim of this was to evaluate differences in histologic and immunohistochemical alterations in rash caused by nib, a dual HER1/2 inhibitor (HER1/2i), and the single HER1 inhibitors (HER1i) cetuximab, erloand panitumumab. erimental Design: For each of the four drugs, skin biopsies were collected and analyzed from ents with rash (n = 32). Blinded independent histologic analysis and automated measurement of n biomarkers involved in proliferation, differentiation, and inflammation were conducted. ults: Increased expression of pAKT and decreased dermal K16 and p27 for HER1/2i when comwith each of the HER1i were observed. In addition, decreased epidermal atrophy and follicular philic infiltrate were evidenced in the skin of patients on HER1/2i when compared with HER1i. clusions: We found a lower inhibition of epidermal kinetics and decreased inflammation in /2i-induced rash. These findings underscore differences in skin toxicity as related to specificity R blockade, concordant with clinical tolerability and decreased severity of skin toxicity seen of HE with the HER1/2i lapatinib compared with the HER1 inhibitors cetuximab, erlotinib, and panitumumab. Clin Cancer Res; 16(17); 4452–60. ©2010 AACR.