Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years.
View Article and Find Full Text PDFBackground: Nivolumab obtained approval in advanced melanoma (AM) with weight-adjusted dose (WAD) administration (3 mg/kg/2 weeks). In 2018, the dosage regimen was changed to flat dose (FD) administration (240 mg/2 weeks or 480 mg/4 weeks) based on a modeling study, without clinical data.
Methods: AM patients have been prospectively included in the French national multicenter MelBase database since 2013.
Background: The Checkmate 067 randomized controlled trial, published in 2015, demonstrated improved progression-free survival and numerically, although not statistically, superior overall survival for ipilimumab + nivolumab. The objective of this study was to compare the efficacy and safety of nivolumab to ipilimumab + nivolumab as first-line treatment for metastatic melanoma in a real-world setting.
Methods: Patients were prospectively included in the French Melbase cohort from 2013 to 2022.
Background: Currently, treatment options for patients with advanced melanoma who experience failed immunotherapy or targeted therapy are lacking. Recent studies suggest the antitumor activity of combined pembrolizumab and lenvatinib in patients with advanced melanoma progressing on immunotherapy. Herein, we report the clinical outcomes of combined lenvatinib and a programmed cell death protein-1 inhibitor (PD-1) in this population.
View Article and Find Full Text PDFBackground: The tumor mutational burden (TMB) is high in melanomas owing to UV-induced oncogenesis. While a high TMB is a predictive biomarker of response to PD-1 inhibitors, it may be associated with the rise of resistant clones to targeted therapy over time. We hypothesized that survivals may depend on both the sun-exposure profile of the site of primary melanoma and the type of systemic treatment.
View Article and Find Full Text PDFBackground: Programmed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity programmed cell death-ligand 1 (PD-L1)-blocking antibody that activates innate and adaptive immunity by blocking PD-L1 interaction with PD-1 and B7-1 receptors.
View Article and Find Full Text PDFBackground: Many classifications exist to select patients with "high-risk" head and neck cutaneous squamous cell carcinoma (HNCSCC).
Objective: To compare the performance of the Brigham and Women's Hospital (BWH) classification with the performance of the American Joint Committee on Cancer 8th Edition (AJCC8), the Union for International Cancer Control 8th Edition (UICC8), and the National Comprehensive Cancer Network (NCCN) classifications.
Methods: In this single-center retrospective study, HNCSCC resected in a tertiary care center were classified as "low-risk" or "high-risk" tumors according to the four classifications.
Nine drugs have been marketed for 10 years for the treatment of advanced melanoma (AM). With half of patients reaching a second line, the optimal sequence of treatments remains unclear. To inform policy-makers about their efficiency, we performed a cost-effectiveness analysis of sequential strategies in clinical practice in France, for BRAF-mutated and wild-type patients.
View Article and Find Full Text PDFBackground: Clinical outcomes of advanced melanoma of unknown primary (MUP) in the era of novel therapies have been scarcely studied.
Objective: To investigate the efficacy and safety of systemic treatments in patients with advanced MUP compared to patients with stage-matched melanoma of known cutaneous primary (cMKP).
Methods: Based on the nationwide MelBase prospective database, this study included advanced melanoma patients treated from March 2013 to June 2021 with first-line immunotherapies, targeted therapies, or chemotherapy.
Purpose: Mitogen-activating protein kinase inhibitors (MAPKis) are largely used in V600E/K BRAF-mutated metastatic melanomas, but data regarding effectiveness of targeted therapy in patients with rare BRAF mutations and molecular description of these infrequent mutations are scarce.
Patients And Methods: A multicenter study was conducted on patients with metastatic melanoma harboring a well-identified mutation of BRAF and enrolled from March 2013 to June 2021 in the French nationwide prospective cohort MelBase. The molecular BRAF mutation pattern, response to MAPKis when applicable, and survival data were analyzed.
Objective: To quantify the risk of immune-related adverse events (irAEs) in patients with pre-existing autoimmune disease (pAID) treated by immune checkpoint inhibitors (ICIs) for stage III or IV melanoma.
Methods: Case-control study performed on a French multicentric prospective cohort of patients with melanoma, matched for irAE risk factors and oncological staging. Risk of irAE was assessed by logistic regression.
Testing for the mutation is mandatory for the management of patients with locally advanced or metastatic melanoma. Molecular analysis based on DNA sequencing remains the gold-standard method for the screening of the different mutations. These methods must be rapid, sensitive, and specific enough to allow optimal therapeutic management in daily practice and also to include patients in clinical trials.
View Article and Find Full Text PDFPigmentation of the human skin is a complex process regulated by many genes. However, only a few have a profound impact on melanogenesis. Transcriptome analysis of pigmented skin compared with analysis of vitiligo skin devoid of melanocytes allowed us to unravel CLEC12B as a melanocytic gene.
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