Background Therapeutic options for BRAFV600-mutant melanoma in patients who progress on BRAF/MEK-inhibitors (BRAF/MEKi) and immune-checkpoint-inhibitor (ICI) therapy, are limited. We conducted a retrospective registry study to investigate post-ICI rechallenge with BRAF/MEKi, stratified by type of initial BRAF/MEKi therapy. Methods This retrospective study analysed patients from the EUMelaReg registry, who received adjuvant or first-line (1L) BRAF/MEKi in the advanced setting, followed by ICI therapy and were later retreated with BRAF/MEKi. Overall response rate (ORR) for rechallenge served as primary endpoint, disease-control rate (DCR), progression-free survival (PFS), and overall survival (OS) were further endpoints. A covariate-matched control group of patients who received BRAF/MEKi only after 1L ICI failure was selected for comparison. Results Among patients previously treated with adjuvant (n=42) or non-adjuvant (n=142) BRAF/MEKi, rechallenge after one interim ICI line resulted in ORRs of 26.2% and 30.3% and DCRs of 42.9% and 61.8%, respectively. Median PFS was 8.4 and 5.1 months, median OS 13.8 and 8.6 months, respectively. Overall, the rechallenge group had a 1-year OS of 43.2%, lower than the matched control (58.9%). The adjuvant subgroup was similar to control (55.4%), while the advanced subgroup showed notably poorer survival (39.9%). Subgroup analyses showed that both the pre-ICI response to BRAF/MEKi treatment and progressive disease prior to ICI were associated with outcome of the BRAF/MEKi rechallenge. Conclusion Rechallenge with BRAF/MEKi therapy under real-world conditions for advanced melanoma provides a valid treatment option. For patients who received their initial BRAF/MEKi therapy as adjuvant therapy there seems to be only limited impairment of outcomes.

BACKGROUND:Encorafenib is a BRAF inhibitor with a pharmacodynamic profile distinct from that of dabrafenib, including a longer dissociation half-life that may enable more sustained BRAF inhibition. It has been hypothesized that this could translate into superior clinical efficacy. We aimed to determine whether encorafenib plus binimetinib is superior to dabrafenib plus trametinib in terms of clinical activity and outcomes. METHODS:Patients were identified through the Danish Metastatic Melanoma Database, a national registry collecting prospective data on systemic treatments. We retrospectively retrieved baseline, treatment, and outcome data for patients with metastatic BRAF-mutant melanoma treated with encorafenib plus binimetinib or dabrafenib plus trametinib from 2017 to 2024. Both unmatched and propensity score-matched analyses were conducted to mitigate potential confounding. RESULTS:A total of 751 patients were included (422 dabrafenib plus trametinib, 329 encorafenib plus binimetinib). Baseline characteristics were balanced between groups. In the unmatched cohort, no statistically differences were observed between dabrafenib plus trametinib and encorafenib plus binimetinib in progression-free survival (PFS; median = 7.9 vs 8.0 months; hazard ratio [HR] = 0.99, P = .90), overall survival (median = 15.5 vs 15.4 months; HR = 0.91, P = .30), or melanoma-specific survival (median = 16.2 vs 15.7 months; HR = 0.94, P = .50). Propensity score-matched analyses confirmed these findings (PFS: HR = 1.05, P = .60; overall survival: HR = 0.922, P = .41; melanoma-specific survival: HR = 0.97, P = .74). Post hoc power analysis for detecting a 3-month survival difference was adequate for PFS (97.5%) but limited for overall survival (56.3%) and melanoma-specific survival (52.1%). CONCLUSIONS:We found no evidence that encorafenib plus binimetinib is superior to dabrafenib plus trametinib in metastatic melanoma. These findings suggest that the choice between these combinations should be guided by tolerability profiles and economic considerations rather than efficacy.

BACKGROUND:Adjuvant anti-PD-1 therapy improves recurrence-free survival in resected stage III melanoma, but its impact on survival remains uncertain. OBJECTIVE:To evaluate the association of adjuvant anti-PD-1 therapy with overall survival (OS) and melanoma-specific mortality (MSM) in patients with stage III melanoma. METHODS:Five-year OS and MSM were compared between stage III melanoma patients diagnosed before (pre-cohort: June 2016-May 2018, n = 450) and after (post-cohort: January 2019-December 2020, n = 552) implementation of adjuvant anti-PD-1 in Denmark. Post-cohort patients receiving adjuvant anti-PD-1 were propensity score-matched to pre-cohort patients. RESULTS:Median follow-up exceeded 5 years in both cohorts. At the population level, no difference in 5-year OS or MSM was demonstrated between the total cohorts. In the post-cohort, 297 patients (53.8%) received adjuvant anti-PD-1. After matching (n = 279 per group), adjuvant anti-PD-1 was associated with higher 5-year OS (80.3% vs. 71.7%; HR 0.67, 95% CI 0.47-0.95; p = 0.022). 5-year MSM estimates were inconclusive (16.6% vs. 20.8%, HR 0.77, 95% CI 0.52-1.14; p = 0.24). Among matched patients with occult nodal disease, results were also inconclusive (OS HR 0.70, 95% CI 0.46-1.06). Sensitivity power analyses indicated that only large effects were detectable given the available events. CONCLUSIONS:We were unable to demonstrate an improved survival at the population level after adjuvant anti-PD-1 introduction, but matched analysis showed higher OS in treated patients. However, uncertainty in disease-specific outcomes and limited power preclude firm conclusions. Mature trial data are essential for defining the role of adjuvant therapy alongside emerging neoadjuvant strategies. Until then, carefully individualized adjuvant treatment decisions are of particular importance.

Background Randomised trials recently showed that sequencing of first-line (1L) immune checkpoint inhibitor (ICI) and second-line (2L) BRAF-MEK-inhibitor (BRAF/MEKi) combination therapy provides better clinical outcomes in BRAFV600-mutated, irresectable/metastatic melanoma than the inverse sequence. However, efficacy benchmark data for 2L BRAF/MEKi are limited as the combination was developed for 1L use, lacking estimates for the impact of prior ICI. Methods This retrospectively study analysed 2,343 patients from the EUMelaReg registry with BRAFV600-mutated melanoma who received BRAF/MEKi either as 2L after failing 1L ICI (n=654) or as 1L treatment (n=1,689). Patients with prior adjuvant ICI or BRAF/MEKi were excluded. Prognostic imbalances between the two groups were adjusted using 1:1 inverse propensity score matching. Key efficacy outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and time on treatment (TOT). Results Patients in the 2L cohort achieved outcomes from start of treatment at least equivalent to the matched 1L BRAF/MEKi cohort. Kaplan-Meier estimates demonstrated longer median PFS (8.4 vs 7.7 months; p=0.01) and longer median TOT (7.8 vs 6.2 months; p=0.002) for patients treated with 2L BRAF/MEKi compared to 1L. Median OS from start of 2L (17.2 months) or 1L (16.0 months) BRAF/MEKi was similar (p=0.73) despite inherent bias from differing index dates. ORR among both groups (56.4% vs 53.5%; p=0.32) was equal. Conclusion This study further supports the recommended sequencing of ICI as 1L and BRAF/MEKi as 2L therapy for patients with BRAFV600-mutated melanoma. It shows that prior failure of ICI does not compromise the efficacy of BRAF/MEKi treatment.

Nivolumab plus ipilimumab has demonstrated activity after anti-PD-1 failure in advanced melanoma, but its effectiveness in later lines and as rechallenge remains unclear. We aimed to characterize outcomes of nivolumab/ipilimumab administered in the third line or beyond. Using the Danish Metastatic Melanoma Database (DAMMED), we identified patients with metastatic melanoma (excluding uveal melanoma) treated with nivolumab/ipilimumab after at least two prior lines of therapy, including adjuvant treatment, between 2017 and 2024. Baseline characteristics, prior treatments, and clinical outcomes were collected. Seventy-three patients were included (median age 57.8 years), of whom 47.9% had brain metastases. Most had progressed on anti-PD-1-based therapy (93.2%); 32.9% had prior exposure to anti-CTLA-4, and 84.9% had received BRAF/MEK inhibitors. Nivolumab/ipilimumab was administered as third-line therapy in 71.2%. After a median follow-up of 27.6 months, the overall response rate was 23.3% (12.5% with prior anti-CTLA-4 exposure vs. 28.6% without). Median duration of response was 19.4 months (95% CI, 14.5-NR). Median PFS was 2.7 months (95% CI, 2.4-5.7) and median OS was 9.6 months (95% CI, 6.5-20.1). In conclusion, in heavily pretreated melanoma, nivolumab/ipilimumab induces durable responses in a minority of patients, with reduced efficacy after prior anti-CTLA-4 exposure.

PURPOSE:Among responders to PD-1/PD-L1 blockade, it remains unclear whether tumour type and traditional baseline patient and tumour characteristics provide additional prognostic information for progression risk beyond response depth. METHODS:In this nationwide, population-based cohort study, we identified adults with metastatic melanoma (MM), renal cell carcinoma (RCC), or non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 monotherapy or dual checkpoint blockade. Analyses were restricted to responders by investigator-assessed RECIST (complete or partial response) with outcomes administratively censored at 5 years. Prespecified baseline and on-treatment variables were evaluated for associations with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox models and assessed for consistency across tumour types. RESULTS:Among 2127 responders, PFS trajectories within response depth categories (complete response and partial response) were highly similar across MM, RCC, and NSCLC. Prespecified variables with prognostic value in the overall population, including performance status and treatment line, provided limited additional prognostic information once response depth was known. Depth of response (complete vs partial) was the strongest independent factor associated with progression risk within each tumour cohort. CONCLUSIONS:Among patients with MM, RCC, or NSCLC who achieved an objective response to PD-1/PD-L1 blockade, tumour type and traditional baseline prognostic factors provided limited additional stratification of progression risk once response depth was known. These findings suggest that, within the tumour types studied, response durability is primarily associated with response depth rather than other known clinical features, supporting prospective evaluation of response-guided follow-up strategies and interventions designed to deepen responses.

INTRODUCTION:The therapeutic benefit of sentinel node biopsy (SNB) for melanoma patients remains controversial. We aimed to evaluate the association between SNB and survival outcomes in a nationwide population-based Danish cohort. MATERIALS AND METHODS:This retrospective cohort study included patients diagnosed with cutaneous melanoma between 2010 and 2017 who were candidates for SNB according to contemporary national guidelines. Augmented inverse probability of treatment weighting (AIPTW) was used to estimate standardized absolute risks and risk differences (RD) for 5-year overall survival, melanoma-specific mortality, other-cause mortality, and recurrence outcomes under two hypothetical strategies: all patients undergoing SNB versus no patients undergoing SNB. RESULTS:Of 6952 eligible patients, 5679 (81.7%) underwent SNB. After AIPTW, the standardized 5-year overall survival was higher under the SNB strategy (82.5% vs 73.7%, RD -8.8 pp, 95% CI -12.0; -5.6), whereas there was no clear difference in melanoma-specific mortality between strategies (9.0% vs 9.8%, RD -0.8 pp, 95% CI -3.0; 1.5). Other-cause mortality was lower under the SNB strategy (8.5% vs 16.8%, RD -8.3 pp, 95% CI -11.1; -5.5). No difference was found for standardized 5-year risk of any recurrence (19.0% vs 18.9%; RD 0.1 pp, 95% CI -3.2; 3.4), nor for distant recurrence. Regional nodal recurrence was lower under the SNB strategy (4.6% vs 8.5%, RD -3.9 pp, 95% CI -6.3; -1.5). CONCLUSION:Since SNB cannot plausibly influence other-cause mortality, our findings indicate residual confounding despite robust adjusted analyses. Observational data such as ours cannot reliably determine whether SNB confers a therapeutic effect.

PURPOSE:Pivotal phase III trials underpin regulatory approval of immunotherapy (IO) and BRAF/MEK inhibitors (BRAF/MEKi) in metastatic melanoma (MM). However, how trial-derived efficacy benchmarks translate into real-world effectiveness across eligibility strata remains insufficiently quantified. METHODS:We conducted a nationwide registry-based cohort study using the Danish Metastatic Melanoma Database, including patients with stage IV MM treated in first line with anti-PD-1 monotherapy, anti-PD-1/anti-CTLA-4, or BRAF/MEKi between 2014 and 2023. Real-world outcomes were compared with reconstructed pseudo-individual patient data from pivotal trials as regulatory efficacy benchmarks. Trial eligibility was defined using key exclusion criteria from pivotal studies. Overall survival (OS), progression-free survival (PFS), and melanoma-specific survival (MSS) were analyzed using Kaplan-Meier and Cox regression methods. RESULTS:Among 1909 patients, 41.7-44.9% of IO-treated and 74.3% of BRAF/MEKi-treated patients were trial-ineligible. In eligible populations, IO outcomes mirrored regulatory benchmarks. In contrast, trial-ineligible patients experienced substantial effectiveness deviations, with significantly higher mortality hazards for anti-PD-1 monotherapy (OS HR 1.61, 95% CI 1.39-1.86; p < 0.001) and nivolumab/ipilimumab (OS HR 1.30, 95% CI 1.02-1.66; p = 0.035) compared to their reference trials. For BRAF/MEKi, real-world outcomes were inferior to regulatory benchmarks even among trial-eligible patients and were markedly worse in trial-ineligible populations, with hazard ratios >2.5 across OS, MSS, and PFS (all p < 0.001). CONCLUSION:Real-world effectiveness of first-line therapies in MM deviates from regulatory trial benchmarks in trial-ineligible populations, with larger discrepancies for BRAF/MEKi than IO. These findings support population-specific effectiveness evaluation to complement trial-based efficacy estimates and inform health-technology assessment and clinical decision-making.

This guideline was developed in close collaboration with multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF) and the European Organization for Research and Treatment of Cancer (EORTC). Recommendations for the diagnosis and treatment of melanoma were developed on the basis of systematic literature research and consensus conferences. Cutaneous melanoma (CM) is the most dangerous form of skin tumor and accounts for 90% of skin cancer mortality. The diagnosis of melanoma can be made clinically and must always be confirmed by dermoscopy. If melanoma is suspected, a histopathological examination is always required. Sequential digital dermoscopy and whole-body photography can be used in high-risk patients to improve the detection of early-stage melanoma. If available, confocal reflectance microscopy can also improve the clinical diagnosis in special cases. Melanoma is classified according to the 8th version of the American Joint Committee on Cancer classification. For thin melanomas up to a tumor thickness of 0.8 mm, no further diagnostic imaging is required. From stage IB, lymph node sonography is recommended, but no further imaging examinations. From stage IIB/C, whole-body examinations with computed tomography or positron emission tomography CT in combination with magnetic resonance imaging of the brain are recommended. From stage IIB/C and higher, a mutation test is recommended, especially for the BRAF V600 mutation. It is important to perform a structured follow-up to detect relapses and secondary primary melanomas as early as possible. A stage-based follow-up regimen is proposed, which in the experience of the guideline group covers the optimal requirements, although further studies may be considered. This guideline is valid until the end of 2026.

INTRODUCTION:Advances in modern therapies have improved outcomes for patients with melanoma brain metastases (MBM), though prognosis remains poor. The optimal treatment strategy for patients who do not meet clinical trial inclusion criteria is unclear. METHODS:This study included all patients with MBM diagnosed in Denmark between 2015 and 2022, identified through the Danish Metastatic Melanoma Database (DAMMED) and local surgical and radiotherapy records. Data were collected from electronic patient records. RESULTS:A total of 838 patients were included, with a median overall survival (OS) of 9.0 months. Of these, 112 (19.4 %) survived beyond 3 years post-diagnosis. Patients treated with immune checkpoint inhibitors (ICI) as first line treatment, specifically ipilimumab + nivolumab, demonstrated an intracranial overall response rate (icORR) of 46 % and a 2-year OS of 49 %. Those treated with BRAF/MEK inhibitors (BRAF/MEKi) had an icORR of 56 % but a 2-year OS of 20 %. Patients with leptomeningeal disease (LMD, n = 67) had a median OS of 8.4 months. Systemic therapy was associated with a superior OS for patients with LMD, though no survival benefit was seen with ICI compared to BRAF/MEKi. Among the 230 patients who underwent surgery, 30 received postoperative stereotactic radiosurgery (SRS); however, there was no difference in OS or intracranial progression-free survival between the groups. CONCLUSION:A considerable proportion of patients with brain metastases diagnosed after 2015 survived more than 3 years. Patients with LMD appeared to obtain limited benefit of ICI with only few patients alive > 3 years post-diagnosis.

A substantial number of patients with metastatic melanoma (MM) treated with anti-PD-1 monotherapy have initial stable disease (SD), yet the real-world prognosis of these patients remains unclear. In this nationwide cohort study, we analysed real-world outcomes of patients with MM treated with pembrolizumab in Denmark. Focusing on patients with initial SD, we assessed best overall response (BOR), progression-free survival (PFS), and overall survival (OS) and identified predictors of survival in multivariable analyses. Out of 1048 included patients, 233 (22.2%) had initial SD with a median PFS and OS of 14.7 and 50.1 months. Subsequent partial response (PR) or complete response (CR) was developed by 44 (18.9%) and 52 (22.3%) patients showing significantly improved PFS compared to patients with continued SD (PR: HR 0.52, 95% CI 0.34–0.81, p = 0.003; CR: HR 0.15, 95% CI 0.07–0.32, p < 0.001) and survival rates comparable to patients with initial PR and CR, respectively. Furthermore, 49 (21.0%) patients showed continued disease control (median follow-up of 82.3 months). For 51.0% of these patients, the last dose of pembrolizumab was administered during SD with a median treatment duration of 12.4 months. Of patients with initial SD, 40% developed a subsequent objective response with improved long-term prognosis comparable to patients with initial response. More than 20% exhibited continued disease control.

BACKGROUND:Intratumoral PD-L1 expression at the 1 % cut-off predicts clinical outcomes and may guide first-line immune checkpoint inhibitor (ICI) selection for metastatic melanoma (MM). However, the impact of the interval between PD-L1 assessment and ICI initiation and the metastatic site used for PD-L1 evaluation, remains unclear. METHODS:In this nationwide cohort study we used the Danish Metastatic Melanoma Database (DAMMED) and the Danish Pathology Registry to analyze patients with MM treated with anti-PD-1 or anti-PD-1 plus anti-CTLA-4 from January 2017 to February 2024. Progression-free survival (PFS) and overall survival (OS) were analyzed using Log-rank tests and Cox regression. RESULTS:Data from 1137 patients were analyzed. Among patients with PD-L1 assessed within 90 days of treatment (n = 964; 55.2 % PD-L1 <1 %, 44.8 % PD-L1 ≥1 %), combination therapy improved outcomes in PD-L1 < 1 % (PFS adjusted (a)HR 0.62; 95 % CI 0.48-0.80; p < 0.001, OS aHR 0.64; 95 % CI 0.48-0.85; p = 0.002), while outcomes were comparable for PD-L1 ≥ 1 % patients (PFS aHR 0.90; 95 % CI 0.62-1.30; p = 0.57, OS aHR 0.97; 95 % CI 0.60-1.57; p = 0.89). For PD-L1 assessed > 90 days prior (n = 173), this pattern was less pronounced. Among 48 paired PD-L1 assessments from the same organ, discordance occurred in 25 %. Combination therapy improved PFS for patients with PD-L1 < 1 % skin/subcutaneous (aHR 0.51; 95 % CI 0.34-0.76; p < 0.001) and visceral metastases (aHR 0.65; 95 % CI 0.42-1.02; p = 0.060) while this association was not evident for lymph node metastases (aHR 0.79; 95 % CI 0.48-1.29; p = 0.35). CONCLUSIONS:PD-L1 seems a reliable predictive biomarker in MM, when assessed on tissue obtained within 90 days prior to ICI initiation. Non-nodal metastatic sites appear preferable.

Background BRAF and MEK inhibitors (BRAFi/MEKi) induce high response rates and rapid tumor regression in BRAF-mutated metastatic melanoma. While responses last around 12 months, ≈ 24 % of patients in clinical trials achieve progression-free survival (PFS) beyond 3 years. The impact of discontinuing therapy after long-lasting responses remains incompletely characterized. Methods We conducted a retrospective nationwide cohort study using the Danish Metastatic Melanoma Database (DAMMED), to include patients with metastatic melanoma treated with BRAFi/MEKi for ≥ 2 years from 2014 to 2022. Survival outcomes were assessed using Kaplan-Meier analyses and the log-rank test. Results 1367 patients initiated treatment with BRAFi/MEKi, 97 received therapy ≥ 2 years, and 37 patients discontinued treatment in the absence of disease progression between 2 and 3.5 years from treatment initiation. Among patients who discontinued, median overall survival was 125 months and median PFS post-discontinuation 14 months. After median follow-up of 49 months post-discontinuation, 24 of 37 patients (65 %) progressed, with 67 % who progressed within 12 months. Of those who progressed, 19 were reinduced with BRAFi/MEKi, achieving a 79 % response rate; mPFS post-reinduction was 25 months (median follow-up 29.4 months). Conclusion In this nationwide real-world cohort of patients with melanoma receiving prolonged BRAFi/MEKi treatment, a notable proportion of patients who discontinued treatment without progression became long-term survivors. Progression after discontinuation typically occurred within the first year, with BRAFi/MEKi-reinduction being highly effective. Treatment discontinuation could be a viable strategy for selected patients, provided close follow-up and prompt reinitiation upon progression. Identifying clinical or molecular features predictive of sustained tumor control remains essential.

Background: BRAF/MEK inhibitors (BRAFi/MEKi) improve outcome in patients with BRAF-mutated metastatic melanoma but are associated with cardiotoxicity, leading to a decline in left ventricular ejection fraction (LVEF). This study aimed to evaluate the incidence, timeline, risk factors, and reversibility of BRAFi/MEKi-induced cardiotoxicity in a real-world setting. Patients/materials and methods: Patients with metastatic melanoma (n = 170) treated with Encorafenib/Binimetinib, Vemurafenib/Cobimetinib, or Dabrafenib/Trametinib at Aarhus and Odense University Hospital, Denmark, from 2015 to 2023 were included. Cardiac function was assessed at baseline and every 3 months during treatment with either echocardiograms or multigated acquisition scans. Cardiotoxicity was defined as a reduction of LVEF by ≥10 percentage points (pp) to an LVEF < 50% (Major cardiotoxicity) or a reduction of LVEF by ≥15 pp but remaining > 50% (Minor cardiotoxicity). Results: Cardiotoxicity occurred in 21% of patients, with 14% experiencing major cardiotoxicity. The mean time to LVEF decline was 187 days, with 92% of major cardiotoxicity cases occurring within the first year. Cardiotoxicity was reversible in 79% of patients following dose reduction, treatment pauses, heart failure therapy, or continued treatment with monitoring. Baseline atrial fibrillation (odds ratio 13.67, p = 0.008) was identified as a risk factor for major cardiotoxicity. Interpretation: BRAFi/MEKi-induced cardiotoxicity is a significant but manageable complication, often reversible with timely interventions. Routine LVEF monitoring is recommended. The majority (92%) of major cardiac events were diagnosed within the first year of treatment, which might warrant a discontinuation of routine LVEF monitoring after 1 year of BRAFi/MEKi treatment.

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.A web-based survey using LimeSurvey was distributed to melanoma experts across 27 European countries from February to April 2022 and updated from February to April 2024. The questionnaire covered the percentage of patients receiving recommended treatments, as well as treatment authorization and reimbursement dates for systemic and adjuvant therapies.There has been significant improvement in the registration and reimbursement of BRAFi/MEKi, anti-PD1, and anti-PD1/anti-CTLA4 therapies, increasing from 48 %, 63 %, and 37 % in 2017 to 96 %, 96 %, and 78 % in 2024, respectively. Despite these gains, restrictions persist. Anti-PD1/anti-CTLA4 combination immunotherapy is still not available without restrictions in 48 % of the surveyed countries. The nivolumab/relatlimab combination is licensed only for PDL-1-negative melanoma and reimbursed in seven countries of Europe. Tebentafusp is reimbursed in 15 countries and talimogene laherpervec in 5. In 2024, adjuvant treatments for stage III melanoma are reimbursed in 22 countries for dabrafenib/trametinib and 24 of 27 for anti-PD1 antibodies. Pembrolizumab and nivolumab are reimbursed in 15 and 8 countries, respectively, for stage IIB/IIC disease.While there have been improvements in the reimbursement of metastatic melanoma treatments in Europe, challenges and discrepancies remain. Further efforts at European and global levels are needed to harmonize and enhance access to cancer medicines.