Mapping the potential for anti-PD-1 therapy in advanced rare skin carcinomas.

This review, focusing on cutaneous adnexal carcinomas, extramammary Paget disease (EMPD), cutaneous angiosarcomas (cAS) and Kaposi sarcoma (KS), summarizes their local recurrence and metastasis rates, tumor mutation burden (TMB), PD-L1 expression, and off-label treatment with systemic anti-PD-1 agents. PD-L1 expression and tumor mutation burden (TMB) were highly variable in adnexal carcinomas (also depending on the histological subtype), cAS and KS tumors, and some responses were noted even in lack of PD-L1 expression or in low-TMB tumors. There were encouraging best overall responses in patients with advanced rare skin carcinomas treated with anti-PD-1 agents in the literature, mostly after failure of other systemic treatments. We identified a total of 3 patients with sebaceous carcinoma (2 with complete response [CR], 1 with partial response [PR]), 5 with porocarcinoma (3 CR, 1 PR, 1 progression of disease [PD]), 2 with spiradenocarcinoma (1 PR, 1 PD), 1 with trichilemmal carcinoma with PR, 9 with EMPD (1 CR, 5 PR, 3 PD), 32 with cAS (5 CR, 18 PR, 9 PD), and 92 with KS (5 CR, 53 PR, 23 SD, 11 PD). However, a large variety of anti-PD-1 agents were used, in monotherapy or in combination with other systemic therapy, in a relatively small number of patients, limiting interpretations on their individual efficacy. The development of clinical guidelines on rare skin carcinomas may provide standardized guidance to physicians towards best care.