Abstract
9556 Background: Melanoma of unknown primary (MUP) account for 3% of all melanomas. Clinical outcome of advanced MUP in the era of novel therapies including immunotherapies (ICI) and targeted therapies (TT) have been only scarcely studied, whereas a possibly different biologic background might introduce changes in its management. Recent retrospective studies suggested that patients with advanced MUP could benefit at least as much from novel therapies as patients with known primary cutaneous melanoma (cMKP). Methods: Based on the nationwide MelBase prospective database (NCT02828202) this retrospective study included patients with advanced melanoma treated with first-line ICI, TT or CT. MUP was defined by upfront occurrence of (sub)cutaneous, nodal and/or visceral metastasis without any known prior or concomitant primary tumor. Patients with primary mucosal or ocular melanoma were excluded. Both progression-free survival (PFS) and overall survival (OS) were analyzed as co-primary variables in MUP vs cMKP, stratified by treatment subset (ICI vs TT vs CT vs whole cohort). Secondary variable was treatment-related toxicity. Multivariate analyses and propensity score analysis were performed. Objective: To investigate the efficacy and safety of systemic treatments (ICI, TT and chemotherapy (CT)) in patients with advanced MUP comparatively to stage-matched cMKP. Results: A total of 1882 patients were analyzed, including 265 (14.1%) MUP. Most patients were treated with first-line ICI. Median follow-up was 16 months. Patients in the MUP cohort more often displayed unfavorable initial prognostic factors (Table). PFS and OS did not significantly differ in MUP compared to MKP patients (p=0.73 and p=0.93 respectively). Stratification of cohorts by treatment type and application of propensity score did not lead to data modification. Treatment-related toxicity rate and severity did not differ between MUP and MKP, regardless of treatment type. Conclusions: Our results suggest that advanced MUP should be managed with similar strategies as advanced MKP. In our cohort, MUP patients benefited from novel therapies as much as MKP patients despite less favorable baseline prognostic factors. Exploratory studies investigating mutational burden and host immunity are needed to identify the underlying mechanisms. [Table: see text]
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