Melanoma of unknown primary: Favorable survival persists in the immunotherapy era.

Abstract

e21513 Background: Patients with advanced melanoma have historically had better survival in those with unknown primary (MUP) than known primary (MKP). Trends in survival since the introduction of immunotherapy have not been established. Methods: We conducted a retrospective cohort study of patients with advanced/metastatic melanoma (Stage IIIC/IV disease) treated during the period 2014-2020 at the University of Louisville. The primary outcome was overall survival in MUP compared with MKP. Differences in clinical characteristics, BRAF status, tumor mutational burden and PD-L1 tumor proportion score (Dako 22C3 assay) were examined. Differences between numerical variables were calculated based on parametric or non-parametric comparisons accordingly and categorical data analyzed using chi-squared testing. Kaplan-Meier survival analyses were performed with log-rank testing to evaluate differences. Alpha was set at 0.05 for significance. Results: Of the 79 patients with advanced/metastatic melanoma included, 12 had MUP and 67 had MKP. Of those with MKP, the primary site was cutaneous melanoma in 65 and anal melanoma in 2. Clinical characteristics showed the majority were male, with median age of 61 years. There were no significant differences in demographics, distribution of stage, BRAF status, TMB, PDL-1 score or treatment modality between MUP and MKP groups (Table). The median follow-up time overall was 50 months. The MUP group demonstrated significantly better survival with 3-year OS of 92% vs. 62% in MKP, and 5-year OS of 83% vs 44% in MKP. Median survival was 54 months for MKP and not reached for MUP. For MKP, the 5-year OS of 44% compares similarly to other cohorts. The Keynote-001 trial of advanced/metastatic melanoma treated with pembrolizumab reported 5-year OS of 41%. This is approximately a 4-fold improvement compared to cohorts treated before the approval of immunotherapy, where the 5-year OS was in the range of 10% [Lee et al, 2009]. The 5-year OS for metastatic MUP was previously in the range of 18%, also suggesting improvement by about 4-fold with the use of immunotherapy. Conclusions: Melanomas of unknown primary continue to have better survival with durable response on immunotherapy even in the advanced/metastatic setting. The exact mechanisms for this survival advantage remain unknown but are likely immune-mediated.[Table: see text]