Comprehensive real-world evidence research in stage III and IV melanoma: Evaluation of a cohort of patients treated at a Portuguese institution.
Authors: Julião Ivo , Cunha Jose Luis , Redondo Patricia , Rodrigues Jessica , Figueiredo Tiago , Manel L Paulo De Sousa Alexandre , Antunes Luis , Freitas Ana Sofia , Moital Ines , Bento Maria José , Borges Marina 
Published: June 2021

e18774

Background: Malignant melanoma (MM) is one of the most aggressive skin cancers and its incidence has been increasing worldwide. Deep understanding of patient characteristics and the course of the disease, specially through the evaluation of real-world evidence, is extremely relevant for an adequate treatment approach and better outcomes. This study aims to comprehensively evaluate demographic and clinical characteristics and also treatment outcomes of patients with stage III and IV MM, treated at a Portuguese institution. Methods: Retrospective cohort study of patients with de novo MM stage III/IV or that evolved from earlier MM stages, between 2015 and 2017 (considered the index date). Patients were followed until 12/31/2019. Demographic, clinical and treatment characteristics were evaluated. Survival was assessed, from the index date, using the Kaplan Meier method and log-rank test to compare groups. Results: We included 215 patients with a median age of 66 years (20-96) and 50.2% (n = 108) were male. At index date, 63.7% (n = 137) were stage III. From those, 41.6% (n = 57) progressed to stage IV during follow-up. At diagnosis, the majority of patients had ulceration (53.3%; n = 119), normal LDH ( < 248 U/L; 56.3%; n = 121) and from 110 patients tested for BRAF, 45.4% (n = 50) had a mutation. In earlier stages, 41.8% (n = 81) performed sentinel LN only and from those 61.7% (n = 50) had latter metastatic disease. Complete LND was performed in 49% (n = 95) and 58.9% (n = 56) had a distant relapse. Brain metastasis were diagnosed in 28.4% (n = 61) of the patients, and 50.8% (n = 31) were not eligible for any treatment due to poor clinical status. Systemic treatment was performed in 70 patients with advanced disease. In 1st line, 34 (48.6%) patients underwent anti-PD-1, 28 (40.0%) BRAF/MEKi, 5 (7.1%) BRAFi and 3 (4.3%) chemotherapy. A 2nd line treatment was performed in 21 (30.0%) patients and 2 (9.5%) underwent 3rd line treatment. With a median follow-up of 29 months OS for all patients at 24 months was 54.9% (95% CI; 48.6-62.0): 69.3% (95% CI; 62.0-77.5) for stage III patients and 29.5% (95% CI; 20.9-41.6) for stage IV patients. OS was worst for known risk factors (ulceration, mitotic rate and LDH). OS at 24 months for patients under systemic treatment was 37.4% (95% CI; 26.9-52.0), with no differences between immunotherapy and targeted therapy. Finally, 22 patients were submitted to limb perfusion with an OS of 58.1% (95% CI; 41.2-81.9) at 24 months and a median PFS of 7.4 months (95% CI; 3.9-11.3). Conclusions: Analysis of real-world data is a solid tool in the evaluation, development and improvement of treatment strategies. Demographic and clinical characteristics are comparable to those of other studied cohorts. Longer follow-up of this population and the inclusion of new patients submitted to contemporary approaches will allow improving knowledge and care for melanoma patients in Portugal.