According to data from recent studies from Europe, a large percentage of patients have restricted access to innovative medicines for metastatic melanoma. Melanoma World Society and European ...Association of Dermato-oncology conducted a Web-based survey on access to first-line recommended treatments for metastatic melanoma by current guidelines (National Comprehensive Center Network, European Society for Medical Oncology ESMO and European Organization for Research and Treatment of Cancer/European Association of Dermato-oncology/European dermatology Forum) among melanoma experts from 27 European countries, USA, China, Australia, Argentina, Brazil, Chile and Mexico from September 1st, 2017 to July 1st, 2018. Data on licencing and reimbursement of medicines and the number of patient treated were correlated with the data on health expenditure per capita (HEPC), Mackenbach score of health policy performance, health technology assessment (HTA), ASCO and ESMO Magnitude of clinical benefit scale (ESMO MCBS) scores of clinical benefit and market price of medicines. Regression analysis for evaluation of correlation between the parameters was carried out using SPSS software. The estimated number of patients without access in surveyed countries was 13768. The recommended BRAFi + MEKi combination and anti-PD1 immunotherapy were fully reimbursed/covered in 19 of 34 (55.8%) and 17 of 34 (50%) countries, and combination anti-CTLA4+anti-PD1 in was fully covered in 6 of 34 (17.6%) countries. Median delay in reimbursement was 991 days, and it was in significant correlation with ESMO MCBS (p = 0.02), median market price (p = 0.001), HEPC and Mackenbach scores (p < 0.01). Price negotiations or managed entry agreements (MEAs) with national authorities were necessary for reimbursement. In conclusion, great discrepancy exists in metastatic melanoma treatment globally. Access to innovative medicines is in correlation with economic parameters as well as with healthcare system performance parameters. Patient-oriented drug development, market access and reimbursement pathways must be urgently found.
•New therapies have dramatically improved the prognosis of metastatic melanoma, but disparities in access to these medicines exist worldwide.•BRAFi+MEKi combinations are fully reimbursed in 17 of 34 (50%) countries.•Anti-PD1 immunotherapies are fully reimbursed in 17 of 34 (50%) countries.•Combination immunotherapy (anti-CTLA4+anti-PD1) is reimbursed in 9 of 34 (26.4%) countries, in 3 countries with restrictions.•Patient-oriented research, development, market access and reimbursement mechanisms must be urgently developed.
Abstract Background Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the ...availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF). Materials and methods Web-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes. Results The recommended BRAF inhibitor (BRAFi) + MEK inhibitor (MEKi) combination was both registered and fully reimbursed in 9/30 (30%) countries, and in 13/30 (43%) (all from Eastern Europe) not reimbursed. First-line immunotherapy with anti-PD1 antibodies was registered and fully reimbursed in 14/30 (47%) countries, while in 13/30 (43%) (all from Eastern Europe) not reimbursed. It was estimated that in Europe 19,600 patients with metastatic melanoma are treated, and 5238 (27%) do not have access to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p < 0.001), health expenditure per capita (r = 0.695; p < 0.001) and the Mackenbach score of health policy performance (r = 0.765; p < 0.001) with the percentage of patients treated with innovative medicines and a number of reimbursed medicines. Conclusions Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma industry.
Background
Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune‐related adverse events ...(IrAEs). Cutaneous IrAEs affect nearly 40% of PD‐1i and 50% of CTLA4i‐treated patients. Severe cutaneous irAE do not often occur but could be life‐threatening and may persist despite treatment discontinuation.
Methods
We aimed to investigate cutaneous IrAEs in a cohort of patients treated with ICI across Europe in an effort to characterize the reactions in a real‐world, phase IV, post‐marketing study using a follow‐up questionnaire.
Data since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow‐up of melanoma and cutaneous adverse events, supported by EADO. The dermatoses reported were pooled into four categories: inflammatory dermatosis, bullous diseases, drug‐related eruptions and pigmentary diseases.
Results
Inflammatory benign dermatoses (n = 63) represented the most common group of reactions (52.5%), followed by drug‐related eruptions (n = 24, 20%), pigmentary diseases (n = 23, 19.2%) and bullous diseases (n = 10, 8.3%). Grade II (n = 41, 34.2%) are represented by bullous pemphigoid, eczema, hypodermitis, lichenoid eruption, maculopapular rash, pruritus, psoriasis‐like rash, urticarial eruption and vitiligo. Grade III (n = 18, 15.0%) are represented by bullous pemphigoid, lichenoid eruption and rashes. Grade IV (n = 2, 1.7%) is only represented by bullous disease. Most cutaneous IrAEs led to immunotherapy continuation (n = 95, 88.0%). CR is associated with more severe the cutaneous irAEs. We report an average time‐to‐onset of 208 days and some late‐onset events.
Conclusion
Our study has characterized the clinical spectrum of cutaneous irAEs, their timing and severity and their relationship with tumour response. Grade I–II cutaneous IrAE are easily managed allowing ongoing anticancer treatment. Severe late‐onset cutaneous irAE are not uncommon. A dermatological follow‐up helps mitigate the risk of life‐threatening adverse events. These findings highlight the importance of oncodermatological involvement in management of patients with melanoma receiving immunotherapy.
ImmunoCobiVem investigated whether a planned switch to atezolizumab after achieving tumour control during run-in with vemurafenib + cobimetinib improves progression-free survival (PFS) and overall ...survival (OS) compared to continuous targeted therapy (TT) in patients with previously untreated advanced BRAFV600-mutated melanoma.
In this multicenter phase 2 study, patients received vemurafenib plus cobimetinib. After 3months, patients without progressive disease (PD) were randomly assigned (1:1) to continue vemurafenib + cobimetinib (Arm A) or switch to atezolizumab (Arm B) until first documented PD (PD1). Primary outcome was PFS1 (time from start of run-in until PD1 or death). OS and safety were also assessed.
Of 185 patients enroled between November 2016 and December 2019, 135 were randomly assigned after the run-in period (Arm A, n = 69; Arm B, n = 66). Median PFS1 was significantly longer in Arm A versus Arm B (13.9 versus 5.9months; hazard ratio HR 0.55; 95% confidence interval CI, 0.37–0.84; PStratified=0.001). Median OS was not reached in either arm (HR 1.22; 95%CI, 0.69–2.16; PStratified=0.389); 2-year OS was higher in Arm B versus Arm A (67%; 95%CI, 53–78 versus 58%; 95%CI, 45–70). Grade 3/4 AEs occurred in 55% of patients in Arm A and 64% in Arm B; treatment-related AEs led to discontinuation of any drug in 7% and 9% of patients, respectively.
In patients with BRAFV600-mutated advanced melanoma who achieve tumour control with TT, early switch at 3months to atezolizumab led to rapid loss of tumour control but provided a numerical OS benefit at 2years compared with continued TT.
•Randomised planned switch from targeted (TT) to immunotherapy prior to progression.•3-month run-in with vemurafenib + cobimetinib followed by atezolizumab versus continued TT.•Switch to Atezolizumab resulted in rapid loss of tumour control in most patients.
ABSTRACT
Vascular thrombosis was found in different proportions of patients with Adamantiades–Behçet's disease (ABD), depending on the ethnicity of the population under study. Various thrombophilic ...factors, including the levels of anticardiolipin antibodies (ACA), were investigated for their role in the thrombotic process with conflicting results. The prevalence of ACA varies considerably in different studies, but their presence has not been associated with increased risk for vascular thrombosis. We present two cases with ABD, deep venous thrombosis (DVT) and elevated levels of ACA that fulfil the criteria for both ABD and antiphospholipid syndrome (APS).
Persistent erythema multiforme: a report of three cases Pavlović, MD; Karadaglić, DM; Kandolf, LO ...
Journal of the European Academy of Dermatology and Venereology,
January 2001, 2001-Jan, 2001-01-00, 20010101, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Three cases of persistent erythema multiforme, two of unknown aetiology and one precipitated by influenza are reported. Lesions were widespread, mostly atypical in appearance and regressed in ...response to immunosuppressants (systemic steroids and/or azathioprine) or, in one case, to dapsone. One patient developed erythroderma responding eventually to etretinate. Histology in all patients was consistent with the mixed, epidermodermal pattern of erythema multiforme. There were no significant laboratory abnormalities nor marked symptomatology apart from itching. The persistent form appears to belong to the spectrum of erythema multiforme being heterogeneous with respect to inducing stimuli, including viral antigens, neoplastic or inflammatory disease or unknown causes. Whenever it is possible, treatment should be adjusted depending on the causative agent.
Objective:
Sentinel lymph node biopsy is the standard of care for nodal staging in clinically node-negative melanoma patients. Our goal was to present 10-year results of sentinel lymph node biopsy at ...our institution and to evaluate the clinicopathologic factors as potential predictors of sentinel lymph node and non-sentinel lymph node metastatic involvement in patients with cutaneous melanoma.
Methods:
We have analyzed clinicopathologic and lymphoscintigraphic characteristics in 420 patients with cutaneous melanoma who underwent sentinel lymph node biopsy between 2010 and 2019. In addition, we have examined the results of group of patients with positive sentinel lymph node biopsy undergoing complete lymph node dissection.
Results:
The overall detection rate of sentinel lymph node biopsies was 97.1%, of which 18.8% was metastatic. Drainage to one regional basin was seen in 345 patients (83.1%) and to multiple drainage regions in 71 patients (17%). In-transit lymph nodes were detected in 20 patients. On univariate logistic regression analysis, male gender, primary tumor thickness with nodular histology, acral location, presence of ulceration, and the number of nodes harvested were significantly associated with sentinel lymph node biopsy status (p < 0.05). On multivariate analysis, the Breslow thickness was the only independent predictor of sentinel lymph node biopsy status. The metastases in non-sentinel lymph node found in 26 patients with positive sentinel lymph node (35.6%) correlated on univariate, as well as on multivariate logistic regression, with tumor subtype and number of sentinel lymph node harvested.
Conclusions:
In addition to the well-established primary tumor thickness as a predictor of sentinel lymph node biopsy positivity, we observed acral location and nodular melanoma subtype to significantly enhance the risk of metastases in sentinel lymph node(s). Primary tumor histology and number of nodes harvested were the only statistically significant variables predicting the non-sentinel lymph node status on multivariate analysis. Lymphoscintigraphy imaging characteristics were not significantly associated with sentinel lymph node status.
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