Overall survival of patients with mucosal melanoma in the US before and after the advent of PD-1 based immune checkpoint inhibitor treatment.

9546 Background: Mucosal melanoma (MM) is a rare, aggressive melanoma subtype with poor survival. Prior to 2010, systemic therapy for MM was limited to chemotherapy, adjuvant interferon, and bolus interleukin-2; after 2015, immune checkpoint inhibitors (ICIs), specifically programmed cell death protein-1 (PD-1) based therapies, were widely adopted. The magnitude of overall survival (OS) benefit from ICIs in MM remains poorly defined. Methods: We conducted a retrospective cohort study of 8,125 patients with histologically confirmed MM from the National Cancer Database. Patients were stratified by diagnosis era (pre-ICI: diagnosed before 2010; post-ICI: diagnosed after 2015) and receipt of first-line systemic therapy (immunotherapy and/or chemotherapy versus none). Survival analysis was conducted using Kaplan-Meier methods and Cox proportional hazards models. Difference-in-differences (DID) models using Cox regression estimated survival improvements attributable to systemic therapy in the post-ICI era. Multivariable logistic regression was fitted to assess changes in the characteristics of patients receiving systemic therapy between eras. Subgroup analysis included metastatic patients and stratification by primary tumor site (genitourinary [GU], gastrointestinal [GI], head and neck [HN]). Covariates for multivariable models were selected a priori based on clinical relevance. Results: Median OS (mOS) significantly improved in the post-ICI era with covariate adjustment (36.2 vs. 25.0 months; HR: 0.63, 95% CI: 0.59-0.66). Adjusted DID analysis demonstrated survival benefits attributable to systemic therapy (HR: 0.86, 95% CI: 0.77-0.97). mOS of metastatic patients also improved in the post-ICI era (12.0 vs. 7.33 months; HR: 0.63, 95% CI: 0.54-0.73). All tumor sites demonstrated significantly longer mOS in the post-ICI era, with GU patients living the longest (49.5 months), followed by HN (34.5 months), and GI (24.4 months). Post-ICI systemic therapy recipients were more likely to be older and publicly insured, to have a high comorbidity burden (Charlson Deyo score), to be ineligible for surgery, and to receive immunotherapy alone compared to pre-ICI patients. Conclusions: Survival of MM patients has improved by 37% since the introduction of ICIs. While OS varies by tumor site, all sites showed relative improvement in the post-ICI era. DID analysis suggested that modern survival benefits are driven by ICIs despite an older and more clinically complex treatment population.