Real-world survival outcomes of patients with de novo stage IV melanoma: A 13-year single center experience.

Abstract

e21526 Background: Survival outcomes of patients with unresectable melanoma improved with the advent of checkpoint inhibitors (ICI) and BRAF/MEK inhibitors. Numerous clinical trials have shown a survival benefit when treated with first-line ICI, but there have been few real-world studies identifying outcomes in purely de novo Stage IV melanoma. We aimed to study long-term survival outcomes in patients with de novo metastatic melanoma. Methods: We conducted a retrospective analysis including adult patients (≥ 18 years) with stage IV melanoma treated at Cleveland Clinic from 1/2010-12/2022. Baseline variables including age, sex, race, smoking history, performance status (ECOG), BRAF mutational status, and serum lactate dehydrogenase were collected along with treatment regimens. Treatment response was assessed using RECIST 1.1 response criteria. Overall survival (OS) and progression-free survival (PFS) were calculated from the diagnosis date. Multivariable Cox regressions were used to estimate associations with OS and PFS. Results: We identified 147 patients with de novo metastatic melanoma at the time of diagnosis. Median age was 65 years, 67% were males, 99% were white, 95% had an ECOG 0-II, and 41% were BRAF mutated. Table 1 summarizes first-line regimens in both groups. Median follow-up was 63 months (range 4.5-145.9). The 2- and 5-year OS for the whole population were 45% (95% CI 38-54) and 28% (95% CI 21-36), respectively. No difference was seen in median OS between BRAF mutated and BRAF wild type (19 vs 21 months, P > 0.05). 60.4% of patients responded to treatment. In a multivariable Cox regression model, Nivolumab (hazard ratio (HR) 2.6, 95% CI 1.24-5.54, p = 0.016) was significantly associated with decreased survival compared to Ipilimumab + Nivolumab but not Pembrolizumab (HR 1.7, 95% CI 0.82-3.46, P = 0.2). In a multivariable Cox regression of BRAF mutated patients, ICI was associated with improved OS compared to BRAF-directed therapy (HR: 0.2, 95% CI: 0.09-0.53, p = < 0.001). In BRAF mutated patients, increased age was also associated with worse OS (HR continuous variable: 1.01, 95% CI: 1.02-1.08, p = 0.002). Conclusions: In patients with stage IV melanoma, ICI regimens showed superior benefits in OS and PFS compared to all other treatments, irrespective of BRAF mutational status. Furthermore, Ipilimumab + Nivolumab was significantly associated with improved OS compared to Nivolumab alone in our population. This real-world data is concordant with prior clinical trials and confirms first-line use of ICI in all patients with metastatic melanoma, with a preference for combined ICI with Ipilimumab and Nivolumab compared to ICI alone. First line regimens in stage IV melanoma. Characteristics BRAF mutated N = 61 BRAF wildtype N = 86 BRAF directed therapy 25 (41%) 0 (0%) Ipilimumab + Nivolumab 16 (26%) 34 (40%) Nivolumab 7 (12%) 10 (11%) Pembrolizumab 4 (1%) 17 (20%) Others 9 (20%) 25 (29%)