Brain metastases from Merkel cell carcinoma: A nationwide retrospective study

Merkel cell carcinoma (MCC) is an aggressive skin cancer causing distant metastases in 30 % of cases but rarely involving the brain. PD-1/PD-L1 inhibitors constitute the standard treatment of advanced MCC but their impact on brain metastases is unknown.

This retrospective study included MCC patients with central nervous system (CNS) metastases from the French CARADERM registry and the Groupe de Cancérologie Cutanée network. Primary objective was to assess CNS metastases incidence. Secondary objectives included response and survival.

Among 1056 MCC patients, CNS metastases incidence was 0.3 % at baseline and 2.6 % throughout the disease course, reaching 7.0 % in stage IV patients. In 37 patients with CNS metastases, median time from diagnosis to CNS metastases was 15.7 months. Extra-CNS metastases preceded CNS involvement (n = 23) with a median delay of 7.3 months. PD-1/PD-L1 inhibitors were administered before (n = 20) and/or after (n = 23) CNS metastases onset. Intra-cranial responses (n = 15) occurred regardless of prior treatment before CNS metastases. Most (9/15) occurred following stereotactic radiosurgery (SRS) plus immunotherapy, with longer median response duration (15.3 months) versus other treatments (5.1 months). Of prior PD-1/PD-L1 complete responders, 4/6 achieved intracranial response. Median OS and PFS after CNS metastases were 6.6 months and 4.7 months, respectively. PD-1/PD-L1 inhibitors and SRS were associated with improved survival in univariate analysis.

CNS metastases are rare, late, and often fatal. PD-1/PD-L1 inhibitors with SRS are likely to constitute the optimal treatment. The quality of response to PD-1/PD-L1 inhibitors prior to CNS metastases predicts intracranial disease control.