Advanced MUP Has Similar Outcomes as Advanced cMKP Despite Poorer Prognosis

Novel therapies benefit patients with melanoma of unknown primary (MUP) to the same degree as those experienced by patients with melanoma of known cutaneous primary (cMKP).

Patients with advanced melanoma of unknown primary (MUP) had similar survival outcomes as patients with melanoma of known cutaneous primary (cMKP) despite poorer prognosis at baseline, according to results of a nationwide study, published in the Journal of the American Academy of Dermatology.

Data for this study were sourced from the MelBase, a prospective database that enrolled patients (N=1882) with advanced melanoma nationwide in France from 2013 through 2021. Trends in treatment and outcomes were compared between patients with MUP (n=265) and cMKP (n=1627). A propensity score matching approach was used to balance for cohort differences.

The MUP and cMKP cohorts comprised patients median age 64 years (range, 18-92) and 66 years (range, 21-97), 62% and 60% were men, 97% and 85% had stage IV disease (P <.001), 38% and 18% had brain metastasis (P <.001), and 48% and 39% had 3 or more disease sites (P =.01), respectively.

The 2 disease cohorts did not differ significantly for first-line treatment strategies. Overall, 65% of patients received immune checkpoint inhibitors, 31% targeted therapy, and 4% chemotherapy.

Our results suggest that advanced MUP should be managed with strategies similar to those for advanced MKP.

After propensity matching, overall progression-free survival (PFS; median, 5.58 vs 5.62 months; P =.73), overall survival (OS; median, 26.9 vs 25.2 months; P =.93), and objective response (P =.36) rates did not differ between the MUP and cMKP cohorts, respectively. For immune checkpoint inhibitor recipients, the objective response rates were 42% and 49% for the MUP and cMKP groups (P =.09), respectively.

However, stratified by treatment strategy, the patients with MUP who received chemotherapy had significantly shorter PFS (median, 2.3 vs 3.0 months; P =.05) and OS (median, 4.0 vs 9.5 months; P =.03) compared with their cMKP counterparts respectively.

Progression-free survival among the MUP group was associated with serum lactate dehydrogenase level (hazard ratio [HR], 2.00; P <.001), metastasis to the central nervous system (HR, 1.49; P <.01), and B-RAF proto-oncogene, serine/threonine kinase (BRAF)-mutational status (HR, 0.56; P <.001). Predictors for OS in the setting of MUP included American Joint Committee on Cancer (AJCC) stage (HR, 2.91; P <.001) and serum lactate dehydrogenase level (HR, 2.25; P <.001).

In all, 70%of patients reported an adverse event, in which 23% had a grade 3 or 4 event. As with survival outcomes, adverse event rates did not differ between disease cohorts (P =.18).

The major limitation of this study was the retrospective design.

Study authors concluded that although patients with advanced MUP had poorer prognosis at baseline, management strategies and outcomes were similar compared with patients who had similar-staged cMKP. “Our results suggest that advanced

MUP should be managed with strategies similar to those for advanced MKP,” they wrote.

Disclosure: Several authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Rousset P, Dalle S, Mortier L, et al. Impact of systemic therapies in metastatic melanoma of unknown primary: a study from MELBASE, a French multicentric prospective cohort. J Am Acad Dermatol. 2022;S0190-9622(22)03142-5. doi:10.1016/j.jaad.2022.11.040