New developments in the biology and the treatment of metastatic Merkel cell carcinoma

Purpose of review: Patients with stage IIIB und IV metastatic Merkel cell carcinoma (mMCC), who are not suitable candidates for surgery or radiotherapy, are unlikely to achieve lasting remission or tumor control by chemo or targeted therapy. In the majority of cases, the tumor arises from viral carcinogenesis associated with the Merkel cell polyomavirus (MCPyV). In MCPyV-negative tumors with a presumable ultraviolet carcinogenesis, a high mutational burden resulting in neoantigens was discovered. In two phase II clinical trials in either the first or second-line setting, a high response rate was observed for immunotherapies with antibodies blocking the programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) immune checkpoints. Recent findings: The response rate was 56% with the anti-PD-1 inhibitor pembrolizumab as a first-line and 32% with the anti-PD-L1 antibody avelumab used as second-line therapy. Both treatments were well tolerated. Treatment response was rapid and in most cases maintained during follow-up, which, however, is still rather short. Whether the MCPyV or the PD-L1 status is predictive for treatment response and progression-free survival is still ambiguous. Additionally, clinical criteria for patient selection for immunotherapy of mMCC have not yet been defined. Summary: PD-1/PD-L1 inhibition can be regarded as new first-line therapy for patients with mMCC not amendable by surgery and/or radiation.

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