An update on access to novel treatment for metastatic melanoma in Europe - A 2024 survey of the European melanoma registry and the European association of dermato-oncology.

Advances in cancer treatments have significantly improved their effectiveness, yet access to first-line therapies remains limited. A 2017 survey revealed that over 25 % of metastatic melanoma patients in Europe lacked access to recommended therapies. To address this, the European Association of Dermato-Oncology and the European Melanoma Registry conducted a follow-up study on the registration and reimbursement of first-line treatments.

Outcomes following long-term disease control with immune checkpoint inhibitors in patients with advanced melanoma.

Immune checkpoint inhibitors (ICI) can achieve durable responses in patients with advanced melanoma, and results from clinical trials suggest cure may be possible for a subset of patients. Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. This study aimed to explore the disease outcomes and survival in a cohort of patients with long-term responses to ICI.

Adjuvant Use of Pembrolizumab for Stage III Melanoma in a Real-World Setting in Europe.

Background: Although data on patients treated with pembrolizumab are available from clinical trials and single-country real-world reports, to our knowledge no multi-country real-world studies have investigated the use of pembrolizumab as an adjuvant treatment for stage III melanoma.

Methods: We used the European Melanoma Registry (EUMelaReg), a disease entity-based registry specific for melanoma, to examine treatment and outcomes for adult patients with stage III melanoma with lymph node involvement who had complete resection and received adjuvant treatment with pembrolizumab. The primary objectives were to describe the demographic and clinical characteristics of the included patients as well as time on adjuvant pembrolizumab treatment (TOT), real-world recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) from adjuvant pembrolizumab initiation.

Patient recruitment into clinical studies of solid malignancies during the COVID-19 pandemic in a tertiary cancer center.

Background And Purpose: To analyze clinical trial activities and patient recruitment numbers into prospective clinical studies for solid malignancies during the COVID-19 pandemic in a tertiary cancer center.

Materials And Methods: Patient recruitment numbers in prospective clinical studies of solid malignancies were retrospectively analyzed for the years 2019 - 2021 at the Comprehensive Cancer Center Zurich (CCCZ). Changes in recruitment numbers were tested for association with organ-specific subunits, as well as organizational and treatment-related trial characteristics.

Nature and management of melanoma recurrences following adjuvant anti-PD-1 based therapy.

Introduction: Approximately 50 % of resected stage II-IV melanoma patients develop recurrent disease by 5 years despite adjuvant anti-PD-1 therapy. Data to define best management of recurrences is lacking.

Methods: This was a multicentre, international, retrospective cohort study.

Infliximab in steroid-refractory immune-related hepatitis does not demonstrate hepatotoxicity and may shorten time on steroids.

Background: Immune-related hepatitis (irHepatitis) is a relatively common immune-related adverse event (irAE) of checkpoint inhibitors. Often, it responds well to steroids; however, in refractory cases, further therapy is needed. Anti-tumor necrosis factor (TNF) antibodies are used for management of multiple irAEs, but there are little data in irHepatitis.

Stringent monitoring can decrease mortality of immune checkpoint inhibitor induced cardiotoxicity.

Background: Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed.

Effects of CTLA-4 Single Nucleotide Polymorphisms on Toxicity of Ipilimumab-Containing Regimens in Patients With Advanced Stage Melanoma.

Single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene, an inhibitor of T-cell priming, are associated with auto and alloimmunity. Studies implied a role for these SNPs as surrogate markers for immunotherapy-outcome in patients with melanoma. However, no predictive SNPs are defined to date.

Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy.

Importance: Acral (AM) and mucosal melanomas (MM) are rare subtypes with a poor prognosis. In those with advanced disease, anti-PD-1 (PD1) therapy has reduced activity compared to that seen in non-acral cutaneous melanoma.

Objective: To determine the efficacy of adjuvant PD1 in resected AM or MM.

Baseline metastatic growth rate is an independent prognostic marker in patients with advanced BRAF V600 mutated melanoma receiving targeted therapy.

Background: Targeted therapy (TT) of BRAF V600 mutated unresectable melanoma with inhibitors of the MAPK pathway achieves response rates of up to 76%, but most patients develop secondary resistance. Albeit TT is strikingly efficacious during the first days of treatment, even in advanced cases, long-term survival is highly unlikely, especially in patients with unfavorable baseline characteristics like elevated lactate dehydrogenase (LDH). In patients treated with anti-PD-1 immune checkpoint inhibitors, elevated baseline metastatic growth rate (MGR) was the most important prognostic factor.

The features and management of acquired resistance to PD1-based therapy in metastatic melanoma.

Background: Anti-PD-1 therapy (PD1) either alone or with anti-CTLA-4 (CTLA4), has high initial response rates, however 20% of patients (pts) with complete response (CR) and 30% with partial response (PR) within 12 months of treatment experience subsequent disease progression by 6 years. The nature and optimal management of this acquired resistance (AR) remains unknown.

Methods: Pts from 16 centres who responded to PD1-based therapy and who later progressed were examined.

Clock-like Mutation Signature May Be Prognostic for Worse Survival Than Signatures of UV Damage in Cutaneous Melanoma.

Novel treatment modalities comprising immune checkpoint inhibitors and targeted therapies have revolutionized treatment of metastatic melanoma. Still, some patients suffer from rapid progression and decease within months after a diagnosis of stage IV melanoma. We aimed to assess whether genomic alterations may predict survival after the development of stage IV disease, irrespective of received therapy.

Cutaneous Adverse Events of Systemic Melanoma Treatments: A Retrospective Single-Center Analysis.

Recent progress in the treatment of advanced melanoma has led to the improved survival of affected patients. However, novel treatments also lead to considerable and distinct skin toxicity. To further characterize cutaneous adverse events (AE) of systemic treatments, we conducted a single-center retrospective study of biopsy-proven cutaneous adverse events of melanoma treatment over a period of 10 years at the University Hospital of Zurich, Switzerland.

Cuticular Poroma: A Rare Poroma Variant Simulating a Malignant Neoplasm That Often Harbors YAP1::NUTM1 Fusions Similar to Their Conventional Counterparts.

Cuticular poroma is a rare variant of poroma composed of exclusively or predominantly cuticular cells, namely of large cells with ample eosinophilic cytoplasm. We report 7 cases of this rare tumor identified among 426 neoplasms diagnosed as poroma or porocarcinoma. The patients were 4 males and 3 females, ranging in age from 18 to 88 years.

Efficacy and toxicity of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy.

Background: In patients with stage III melanoma, despite surgical resection and adjuvant systemic therapy, locoregional recurrences still occur. The randomized, phase III Trans-Tasman Radiation Oncology Group (TROG) 02.01 trial demonstrated that adjuvant radiotherapy (RT) after complete lymphadenectomy (CLND) halves the incidence of melanoma recurrence within local nodal basins without improving overall survival or quality of life.

Impact of Covid-19 on the management of patients with metastatic melanoma.

The Covid-19 pandemic created new uncertainties in the management of metastatic melanoma patients. In particular, the impact of immunotherapy, targeted therapy, or chemotherapy on the risk of Sars-CoV-2 infection and severity was debated. In this study, we analyzed all patients with metastatic melanoma receiving therapy who developed Covid-19 between February 2020 and February 2022.

Real-world outcomes using PD-1 antibodies and BRAF + MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland.

Background: Programmed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland.

Maximal surgical tumour load reduction in immune-checkpoint inhibitor naïve patients with melanoma brain metastases correlates with prolonged survival.

Background: Recent therapeutic advances in metastatic melanoma have led to improved overall survival (OS) rates, with consequently an increased incidence of brain metastases (BM). The role of BM resection in the era of targeted and immunotherapy should be reassessed. In the current study we analysed the role of residual intracranial tumour load in a cohort of melanoma BM patients.

Treatment reality of patients with BRAF-mutant advanced/metastatic melanoma in Switzerland in the era of choice.

Cutaneous melanoma represents a major cause of cancer death in Europe. Without adequate therapy, the 5-year survival rate is 15-20% in distant metastatic disease. Evaluating the status quo of treatment standards in advanced melanoma and rationale for therapy decisions in Switzerland between January 2016 and September 2018.