Title: Characterization of Melanoma of Unknown Primary in the Era of Immunotherapy and Targeted Therapy in Spain: Results from the Prospective Real World Study GEM 1801.

BACKGROUND

The clinical presentation of melanoma of unknown primary (MUP) and its treatment patterns remain incompletely characterized.

METHODS

GEM1801 is a prospective, observational study in Spain enrolling patients with advanced melanoma. This analysis describes the clinical features and outcomes of patients with MUP.

RESULTS

From August 2018 to December 2022, 893 evaluable patients were enrolled, of whom 133 (14.9%) had MUP. Median age was 63 years (range 24-93); 81 (60.9%) were men; 117 (88.0%) had distant metastases; lactate dehydrogenase (LDH) was elevated in 50 (37.6%); and 79 (54.9%) had BRAF-mutated tumors. Compared with patients with a known primary, immunotherapy was prescribed less frequently (adjuvant: 15.5% vs 27.2%, p = 0.007; first-line metastatic: 53.6% vs 64.0%, p = 0.039). Median progression-free survival (PFS) was 18.9 months (95% CI: 4.4-NR), 13.3 months (95% CI: 7.1-27.5), and 6.7 months (95% CI: 3.5-NR), and median overall survival (OS) was 24.9 months (95% CI: 24.1-NR), 13.9 months (95% CI: 8.3-NR), and 17.9 months (95% CI: 9.6-NR) in patients with BRAF-mutated tumors treated with immunotherapy, BRAF-mutated tumors treated with targeted therapy, and BRAF-wild-type tumors treated with immunotherapy, respectively.

CONCLUSIONS

In Spain, MUP is characterized by multi-organ involvement and frequent brain metastases and was associated with worse outcomes than the overall melanoma cohort. A diagnosis of MUP appears to influence treatment allocation, particularly regarding immunotherapy. When stratified by BRAF status and treatment type, no survival differences were observed between MUP and melanoma of known primary, except for OS among patients with MUP and BRAF-mutated tumors treated with immunotherapy. CLINICAL TRIAL IDENTIFICATION: clinicaltrials.gov: NCT03605771.