2-9% of patients diagnosed with an advanced melanoma have no known primary (MUP). Since MUP and melanom of known primary (MKP) have similar UV-induced mutations and molecular signatures it is proposed that the primary tumour has regressed completely in patients with MUP. As this could be indicative of an enhanced recognition of melanoma antigens, we hypothesize that patients with advanced MUP have a better outcome compared to MKP.
Patients with advanced MUP from 10 German university hospitals were retrospectively analysed and matched with MKP based on type of systemic treatment (BRAF- and MEK-inhibitor, PD-1 inhibitor monotherapy, combined CTLA-4 and PD-1 inhibitor therapy) therapy line (first or second line) and AJCC stage (IIIC, IV M1a-M1d). 337 patients with MUP were identified and 152 treatments with PD-1 and CTLA-4 inhibitor, 142 treatments with PD-1 inhibitor and 101 treatments with BRAF and MEK inhibitor were evaluated. Median PFS was significantly prolonged in MUP patients treated with PD-1 monotherapy (17 months, p=0.002) compared to MKP (5 months) as well as in MUP treated with combined PD-1 and CTLA-4 therapy (11 months, p<0.0001) compared to MKP (4 months). PFS under BRAF and MEK inhibitors was not significantly different in the MKP group compared to the MUP cohort. Moreover, the occurrence of immune related adverse events upon treatment with immune checkpoint inhibitors (ICI) was comparable in the MKP and MUP cohort.
In our multicentre collective, patients with MUP have better outcomes under therapy with ICI compared to MKP.