Clinical features and response to systemic therapy in a historical cohort of advanced or unresectable mucosal melanoma

Abstract

There are very few data available regarding the pattern of first metastases in resected mucosal melanomas (MMs) as well as the response of advanced MM to cytotoxic therapy. A retrospective, single-institution cohort was assembled of all patients with advanced/unresectable MM between 1995 and 2012 who had received systemic therapy with available imaging (N=81). Responses to first-line and second-line systemic therapy were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The relationship between response, overall survival, and clinical covariates was investigated using Cox proportional hazards regression. Primary sites included anorectal (N=31, 38%), vulvovaginal (N=28, 35%), head and neck (N=21, 26%), and gallbladder (N=1, 1%) mucosa. Seven percent of patients had their first relapse in the brain. Cytotoxic therapy represented 82 and 51% of first-line and second-line regimens. The best response achieved in the first-line setting was similar for single-agent [10%; 95% confidence interval (CI): 1-32%] and combination alkylator therapy (8%; 95% CI: 2-21%). Median overall survival from first-line treatment was 10.3 months (95% CI: 8.7-13.9 months). Patients with elevated lactic dehydrogenase [hazard ratio (HR): 1.87, 95% CI: 1.10-3.19, P=0.020] and Eastern Cooperative Oncology Group performance status 1-2 (HR: 1.69, 95% CI: 1.05-2.72, P=0.030) had a higher risk of death, whereas patients with 12-week objective responses had a lower risk of death (HR: 0.12, 95% CI: 0.04-0.41, P<0.001). Cytotoxic systemic therapy has modest activity in advanced/unresectable MM, belying its adjuvant benefit. Patients whose tumors have an objective response to therapy have a lower probability of death. Brain imaging should be considered in routine surveillance.

Figure 1

Circos plot of all initial metastatic sites (n=143) for 76 patients. The 143 sites are broken down by primary site on the left half of the circle and the metastatic organ on the right half, with the segments representing the relative abundance of metastases by primary site and destination. Ribbons connect the primary site with the metastatic organ system, with the color corresponding to the primary site associated with that colored segment (e.g. anorectal, blue) and the width denoting the number of cases that metastasized to that site (e.g. anorectal spread to liver, n=16). Relative percentages of spread are represented on the outer segments; for example, 36% of anorectal metastases were to the liver (red, 11 o’clock) and 67% of bone metastases originated from the head and neck (purple, near 6 o’clock).

Figure 2

Overall survival from initiation of first systemic treatment by primary site. Overall OS was 10.3 months (95% CI 8.7–13.9 months).There was no significant difference in median OS for tumors arising from the anorectal, head and neck, and vulvovaginal regions (p=0.57, log-rank test).