OBJECTIVES:  This retrospective study examined therapeutic outcomes to first-line (1L) chemotherapy in patients with distant metastatic Merkel cell carcinoma (mMCC). MCC is a rare, aggressive skin cancer associated with poor prognosis in patients with metastatic disease. Advanced MCC is typically treated with chemotherapy, but there is no approved standard-of-care treatment. METHODS:  Data were obtained from the US Oncology Network/McKesson Specialty Health electronic health record database and medical charts. Qualifying patients were adults with distant mMCC who had received 1L chemotherapy between 11/2004 and 9/2014 with follow-up until 6/2015. Patients who received treatment with any drug targeting T-cell coregulatory proteins were excluded, among other eligibility criteria. Objective response rate (ORR) to 1L chemotherapy was assessed using RECIST v1.1 as a guide, and duration of response (DOR), time to treatment discontinuation (TTD), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier methodology. The primary analysis population was patients with immunocompetent status. RESULTS:  Of 686 patients identified to have MCC, 67 qualified for analysis (76% immunocompetent/24% immunocompromised). In immunocompetent patients (n=51) at start of 1L chemotherapy, median age was 78 years, 84% were male, 49% had an ECOG performance status of 1, and 69% were diagnosed initially with stage I-III disease. The most common 1L regimen was carboplatin + etoposide (63%). ORR was 29.4% (95% CI, 17.5–43.8), median DOR was 6.7 mos (95% CI, 1.2–10.5; interquartile range, 2.3–12.1), median TTD was 2.4 mos (95% CI, 2.2–2.9), median PFS was 4.6 mos (95% CI, 2.8–7.7), and median OS was 10.5 mos (95% CI, 7.2–15.2). Results in the overall population were consistent with those in the immunocompetent population. CONCLUSIONS:  In patients with distant mMCC treated with 1L chemotherapy, responses were of limited duration. The median survival was less than 1 year, highlighting the need for novel therapies.