Brain metastases from Merkel cell carcinoma: A nationwide retrospective study

Merkelcell.org Summary

Merkel cell carcinoma (MCC) is a rare skin cancer that spreads far in about 30% of patients. However, it rarely spreads to the brain, so doctors don’t know much about the best way to treat brain metastases.

This study looked at 1,056 MCC patients in France and found that 37 patients (3.5%) developed brain metastases. These patients were more likely to be younger, male, and already have MCC that had spread to other parts of the body. On average, brain metastases appeared about 16 months after the first MCC diagnosis, usually after other metastases had already been found. Once a brain metastasis was diagnosed, average survival was 6.6 months in this group of patients.

Of the 37 patients, 23 received immunotherapy, a drug that helps the immune system fight cancer. 8 patients also received stereotactic radiosurgery, a special type of focused radiation often used to treat brain tumors. Patients who got both immunotherapy and stereotactic radiosurgery responded the best, with their disease controlled for an average of 15.3 months, compared to only 5.1 months for patients on other treatments.

This study highlights that while brain metastases from MCC are rare, they are serious and can be difficult to treat. Though more research is needed, the results suggest that a combination of immunotherapy and stereotactic radiosurgery may be the most effective treatment for MCC brain metastases. However, not all patients can tolerate both treatments. For some, one therapy or a different type of treatment may work better. This makes it important to have an individualized discussion with their doctor.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Brain metastases; Immune checkpoint inhibitors; Immunotherapy; Merkel cell carcinoma; Metastases; Skin cancer; Stereotactic radiosurgery.