Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry

Abstract

Background: The incidence of metastatic melanoma is increasing in all ages. Multiple trials with targeted drugs and immune checkpoint inhibitors showed improved survival in metastatic melanoma. However, patients aged ≥75 years are often under-represented in clinical trials, therefore raising questions on safety and efficacy of treatment. Patients and methods: We analyzed a real-world cohort of 3054 patients with metastatic melanoma stratified for age (≤65 years, 66-74 years and ≥ 75 years), and BRAF status, providing data on treatment strategies, toxicity, and survival. Kaplan Meier curves and Cox Proportional Hazard Models were used to present overall survival (OS) and Melanoma Specific Survival (MSS). Results: Overall, 52.2% of patients were ≤ 65 years and 18.4% of patients ≥75 years. BRAF mutated tumors were found less often in patients ≥75 years: 34.5% versus 65% in patients ≤65 years. Patients ≥75 years received systemic therapy less frequently compared to their younger counterparts independent of the BRAF status. When receiving treatment, no statistical significant difference in grade 3 or 4 toxicity was observed. Three year Overall Survival rate was 13.7% (9.1-19.3) in patients ≥75 years versus 26.7% (23.1-30.4) in patients ≤65 years, with a Hazard Ratio (HR) of 1.71 (95%CI 1.50-1.95), p < 0.001. Three year Melanoma Specific Survival was 30.4% (22.0-39.2) versus 34.0% (29.7-38.2), HR 1.26 (95% CI 1.07-1.49), p = 0.005 with an adjusted HR of 1.21 (1.00-1.47), p = 0.049. Conclusion: Patients with metastatic melanoma ≥75 years are less frequently treated, but when treated there is no statistical significant increase in toxicity and only a borderline statistical significant difference in Melanoma Specific Survival was seen, compared to younger patients.

Population Mortality in Advanced Melanoma Patients with and Without Response and Progression; Data from the Dutch Melanoma Treatment Registry

“…We argue that the effect of age is strong, even after correcting for risk factors. This has been shown in a previous study by Jochems et al [22], where the difference in unadjusted and adjusted hazard ratio of age for death was small. Possibly, this is caused by the mix of risk factors: in our study, older patients have significantly worse ECOG PS but significantly less brain metastases and lower disease stage and less organ sites with metastases (Supplement 4).…”

“…Other explanations might be that patients have lived healthier after diagnosis with advanced melanoma, with better outcomes than the general population as a result. Previous studies of Jochems et al [22] and de Glas et al [23] studied outcomes of systemic therapy in older patients with metastatic melanoma. The study of Jochems et al used a registered variable for cause of death, and found borderline significance in 3-year melanomaspecific mortality between patients aged 60 years and !75 years.…”