Cytotoxic chemotherapy is commonly used to treat advanced Merkel cell carcinoma (MCC). However, its efficacy in distant metastatic MCC patients is unclear, in part because most prior reports aggregated these patients with those receiving adjuvant chemotherapy and combined chemoradiation for whom prognosis and outcomes may differ. In this retrospective study, we analyzed detailed records from 62 patients with distant metastatic MCC treated with cytotoxic chemotherapy. Efficacy outcomes including response rate (RR), durability of response (DOR), progression‐free survival (PFS), and overall survival (OS) were evaluated. In this cohort, platinum plus etoposide was the most commonly used first‐line regimen (69%). RR to first‐line chemotherapy was 55% (34/62) with complete responses (CR) in 13% (8/62) and partial responses (PR) in 42% (26/62) while 6% (4/62) had stable disease and 39% (24/62) had progressive disease. Median PFS was 94 days and median OS was 9.5 months from start of chemotherapy. Among responding patients (n = 34), median PFS was 168 days and median DOR was 85 days. Among 30 of the 62 patients who received second‐line chemotherapy, RR was 23% (7/30; 1 CR, 6 PR), median PFS was 61 days, and median DOR was 101 days. In summary, first‐line chemotherapy is associated with a high RR in metastatic MCC, but responses are typically not durable, and the median PFS is only 3 months. These results suggest rapid emergence of chemoresistance in MCC tumors, and may serve as a useful comparator for immunotherapies currently being explored for metastatic MCC.

Background Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases/year in the USA, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV-oncoprotein (T-antigens) have been correlated with MCC tumor burden. We prospectively validated the clinical utility of MCPyV oncoprotein antibody titers for MCC prognostication and surveillance. Methods MCPyV-oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly-diagnosed MCC were followed prospectively (median follow-up 1.9 years). Among seropositive patients, antibody titer and disease status were serially tracked. Results Antibodies to MCPyV-oncoproteins were rare among healthy individuals (1%) but present in most MCC patients (114 of 219, 52%, p<0.01). Seropositivity at diagnosis independently predicted decreased recurrence risk (HR=0.58; p=0.04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. Following initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 timepoints), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence while a decreasing titer had a negative predictive value of 97%. Conclusions Determination of oncoprotein antibody titer assists in the clinical management of newly diagnosed MCC patients by stratifying them into a higher risk seronegative cohort in whom radiologic imaging may play a more prominent role, and into a lower-risk seropositive cohort whose disease status can be tracked in part via oncoprotein antibody titer.

Skin directed therapies (SDTs) serve important roles in the treatment of early stage cutaneous T-cell lymphoma (CTCL)/mycosis fungoides (MF), as well as managing symptoms and improving quality of life of all stages. There are now numerous options for topical therapies that demonstrate high response rates, particularly in early/limited MF. Phototherapy retains an important role in treating MF, with increasing data supporting efficacy and long-term safety of both UVB and PUVA as well as some newer/targeted methodologies. Radiation therapy, including localized radiation and total skin electron beam therapy, continues to be a cornerstone of therapy for all stages of MF.

Summary Background Merkel cell carcinoma (MCC) is an aggressive, high‐grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low‐ and moderate‐grade NETs that express somatostatin receptors (SSTRs). Objectives To assess SSTR expression and the efficacy of SSAs in mMCC, a high‐grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression‐free survival (PFS) of ≥ 120 days after initiation of SSA. Results Thirty‐three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response‐evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152–358). Twelve of 19 patients did not have a response‐evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143–1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. Conclusions In contrast to other high‐grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side‐effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.

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