Study: Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021. Image Credit: Africa Studio/Shutterstock.com
The outlook for advanced melanoma, encompassing unresolvable stage III and IV cases, has markedly improved due to the advent of novel treatments.
Starting with the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) blocking antibody ipilimumab in 2012, the treatment landscape expanded to include B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitors for patients with BRAF-mutant melanoma in 2012, anti-Programmed Cell Death (PD)-1 antibodies in 2015, and combinations of BRAF inhibitors with Mitogen-Activated Protein Kinase (MEK) inhibitors and ipilimumab with nivolumab in 2016.
Recent advancements also introduced therapies such as Lymphocyte-Activation Gene 3 (LAG-3) antibodies and Tumor-Infiltrating Lymphocyte (TIL) therapy. In the Netherlands, survival rates have risen following these innovations, even outside clinical trials.
Further research is needed to understand the factors driving the recent decline in survival rates and to develop strategies to improve outcomes for advanced melanoma patients, particularly in the coronavirus disease 2019 (COVID-19) pandemic and evolving treatment modalities.
About the study
The data for the present study was sourced from the Dutch Melanoma Treatment Registry (DMTR). They involved patients aged 18 and over diagnosed with advanced melanoma from 2013 to 2021, specifically focusing on those who received systemic treatment.
These patients were categorized based on the year their melanoma was diagnosed as unresectable.
Those who progressed to unresectable disease following neoadjuvant or adjuvant treatments were included from the point they commenced treatment for their unresectable condition. Exclusions were made for patients with uveal or mucosal melanoma.
Patient demographics and tumor characteristics at the point of advanced disease diagnosis – including age, gender, performance status, lactate dehydrogenase levels (LDH) levels, melanoma location and type, thickness, ulceration presence, liver and brain metastases, number of metastatic organ sites, American Joint Committee on Cancer (AJCC) 8th edition staging, and mutation status were carefully recorded. The study also differentiated between synchronous and metachronous presentations of melanoma.
Statistical analysis was conducted using various methods to compare baseline characteristics and to estimate median survival times and the impact of the year of diagnosis on overall survival.
This involved descriptive statistics, Pearson’s chi-squared, and t-tests for categorical and continuous variables, respectively. Survival analysis was performed with the Kaplan-Meier method, and the Cox proportional hazards model was applied for multivariable analysis, considering several factors identified from previous research.
Statistical computations were performed using R software and several packages for data manipulation and analysis, ensuring a comprehensive and rigorous statistical examination of the collected data.
Between 2013 and 2021, the DMTR recorded 7,928 patients with advanced melanoma. After excluding cases of uveal and mucosal melanoma, 7,317 patients were included in the analysis.
Many of these patients received systemic treatment, increasing from 74% in 2013 to 86% in 2020 and slightly decreasing to 83% in 2021.
Out of those treated, 6,260 patients were included after further exclusions for uveal and mucosal melanoma. Among these, 428 had received neoadjuvant or adjuvant treatment before their systemic treatment for advanced melanoma.
The study observed a median follow-up of 50.9 months, with the longest follow-up for the 2013 cohort at 106.0 months and the shortest for the 2021 cohort at 14.1 months.
The median age of patients diagnosed with advanced melanoma increased over the years, and there was a noticeable rise in the number of patients with poor performance status and brain metastases. Interestingly, the prevalence of synchronous metastatic disease also increased, particularly in 2020 and 2021.
Treatment modalities evolved from BRAF inhibitors and ipilimumab monotherapy to BRAF/MEK inhibitors, anti-PD-1 antibodies, and combination therapies. The study also noted changes in the duration of these treatments over time.
The median OS for systemically treated advanced melanoma patients improved from 11.2 months in 2013 to 32.0 months in 2019.
However, a decline was observed in patients diagnosed in 2020 and 2021, with median OS dropping to 26.6 and 24.0 months, respectively, although these decreases were not statistically significant.
This trend was mirrored in the melanoma-specific survival (MSS) data, with improvements seen until 2019, followed by a decrease for the cohorts of 2020 and 2021.
Furthermore, the study found that neoadjuvant and adjuvant treatments did not significantly affect survival outcomes for advanced melanoma. Patients with synchronous metastases had shorter survival than those with metachronous metastases.
Despite treatments improving survival post-2013, a concerning trend of increased mortality risk was noted for diagnoses in 2020 and 2021, underscoring the urgency for ongoing research and treatment adaptation.