Clinicopathological evaluation of skin lesions (SL) in patients with hepatocellular carcinoma (HCC) treated with sorafenib

Background: Dermatologic adverse events (DAE) are frequently experienced in patients under sorafenib. Although the majority appear as rash or hand-foot reaction, some patients may present SL requiring biopsy or local procedures that may impact in the treatment. While there are series of patients with melanoma and BRAF inhibitors presenting SL, there is no information on HCC patients with sorafenib.
Methods: We analyzed a prospective database of patients with HCC treated with sorafenib. Patients who developed biopsed SL were included and the pathology samples were reviewed.
Results: Between oct-2007 and jan-2018, 313 patients were treated with sorafenib (54.6% BCLC-C, 88.7% ECOG-PS0 and 83.6% CPA), 88 (28.1%) presented DAE in the first 60 days (eDAE) and 24 (7.7%) developed SL submitted to excisional biopsy. From the 24 patients, 33 SL were biopsied and 5 patients presented more than 1 SL. Most of the patients with SL were male (79.2%), CPA (87.5%), HCV etiology (87.5%) and 2 had liver transplantation. The median time from sorafenib initiation until SL biopsy was 8.5 months (IQR 4.4 to 18.1). SL are described in the table. Lymphocyte proliferation at the interface between the SL and dermis was noted in 61.1%. The median treatment duration (MTD) and OS in the whole cohort were 6.5 months [IQR 3.3-13.9] and 13.6 months [CI95% 12.2- 15.6], respectively. For the subgroup with SL, the MTD and OS was 12.5 [9.5 - 22.0] and 26.5 months [CI95% 17.0 - 43.9], respectively. For those with both eDEA and SL, the MTD and OS was 17.9 months [7.7-28.9] and 26.5 [22.0-51.6] respectively. There was no permanent discontinuation related to the SL.