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1دورية أكاديمية
المؤلفون: Mandel-Brehm, Caleigh, Vazquez, Sara E, Liverman, Christopher, Cheng, Mickie, Quandt, Zoe, Kung, Andrew F, Parent, Audrey, Miao, Brenda, Disse, Emmanuel, Cugnet-Anceau, Christine, Dalle, Stéphane, Orlova, Elizaveta, Frolova, Elena, Alba, Diana, Michels, Aaron, Oftedal, Bergithe E, Lionakis, Michail S, Husebye, Eystein S, Agarwal, Anil K, Li, Xilong, Zhu, Chengsong, Li, Quan, Oral, Elif, Brown, Rebecca, Anderson, Mark S, Garg, Abhimanyu, DeRisi, Joseph L
المصدر: Diabetes. 72(1)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Immunology, Immunotherapy, Women's Health, Clinical Research, Rare Diseases, Autoimmune Disease, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Humans, Animals, Mice, Perilipin-1, Autoantibodies, Lipodystrophy, Congenital Generalized, Lipodystrophy, Adipose Tissue, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
الوصف: Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking. Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte-specific lipid droplet protein perilipin 1 (PLIN1) in a murine model of autoimmune polyendocrine syndrome type 1 (APS1). We then tested for PLIN1 autoantibodies in human subjects with acquired lipodystrophy with two independent severe breaks in immune tolerance (including APS1) along with control subjects using a specific radioligand binding assay and indirect immunofluorescence on fat tissue. We identified autoantibodies to PLIN1 in these two cases, including the first reported case of APS1 with acquired lipodystrophy and a second patient who acquired lipodystrophy as an immune-related adverse event following cancer immunotherapy. Lastly, we also found PLIN1 autoantibodies to be specifically enriched in a subset of patients with acquired generalized lipodystrophy (17 of 46 [37%]), particularly those with panniculitis and other features of autoimmunity. These data lend additional support to new literature that suggests that PLIN1 autoantibodies represent a marker of acquired autoimmune lipodystrophies and further link them to a break in immune tolerance.
وصف الملف: application/pdf
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2دورية أكاديمية
المؤلفون: Ruiz, Lucie, Gurlo, Tatyana, Ravier, Magalie A, Wojtusciszyn, Anne, Mathieu, Julia, Brown, Matthew R, Broca, Christophe, Bertrand, Gyslaine, Butler, Peter C, Matveyenko, Aleksey V, Dalle, Stéphane, Costes, Safia
المصدر: Cell death & disease. 9(6)
مصطلحات موضوعية: Animals, Mice, Inbred C57BL, Humans, Diabetes Mellitus, Melatonin, Proteasome Endopeptidase Complex, Glucose, Receptors, Melatonin, Histones, RNA, Messenger, Inflammation Mediators, Cytokines, Signal Transduction, Apoptosis, Acetylation, Male, Insulin-Secreting Cells, E1A-Associated p300 Protein, Proteolysis, Diabetes, Genetics, 2.1 Biological and endogenous factors, Metabolic and Endocrine, Mice, Inbred C57BL, Receptors, RNA, Messenger, Oncology and Carcinogenesis, Biochemistry and Cell Biology
الوصف: In type 2 diabetes, amyloid oligomers, chronic hyperglycemia, lipotoxicity, and pro-inflammatory cytokines are detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The histone acetyl transferase p300, involved in remodeling of chromatin structure by epigenetic mechanisms, is a key ubiquitous activator of the transcriptional machinery. In this study, we report that loss of p300 acetyl transferase activity and expression leads to beta-cell apoptosis, and most importantly, that stress situations known to be associated with diabetes alter p300 levels and functional integrity. We found that proteasomal degradation is the mechanism subserving p300 loss in beta-cells exposed to hyperglycemia or pro-inflammatory cytokines. We also report that melatonin, a hormone produced in the pineal gland and known to play key roles in beta-cell health, preserves p300 levels altered by these toxic conditions. Collectively, these data imply an important role for p300 in the pathophysiology of diabetes.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/9894r9hvTest
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3دورية أكاديمية
المؤلفون: Kandel, Marguerite, Bardet, Aurélie, Dalle, Stéphane, Allayous, Clara, Mortier, Laurent, Guillot, Bernard, Dutriaux, Caroline, Leccia, Marie-Thérèse, Dalac, Sophie, Montaudié, Henri, Saiag, Philippe, Legoupil, Delphine, Brunet-Possenti, Florence, Arnault, Jean-Philippe, Quatrebarbes, Julie, Beylot-Barry, Marie, Maubec, Ève, Lesimple, Thierry, Aubin, François, Grob, Jean-Jacques, Granel-Brocard, Florence, Stoebner, Pierre-Emmanuel, Dupuy, Alain, Dréno, Brigitte, Michiels, Stefan, Lebbe, Céleste, Borget, Isabelle
المساهمون: Institut Gustave Roussy IGR, Oncostat U1018 (Équipe 2), Centre Léon Bérard Lyon, Immunologie humaine, physiopathologie & immunothérapie HIPI (UMR_S_976 / U976), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 ONCO-THAI, Centre Hospitalier Régional Universitaire Lille CHRU Lille, Centre Hospitalier Universitaire de Bordeaux CHU de Bordeaux, Centre Hospitalier Universitaire Grenoble CHU, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Nice CHU Nice, Hôpital Ambroise Paré AP-HP, Centre Hospitalier Régional Universitaire de Brest CHRU Brest, AP-HP - Hôpital Bichat - Claude Bernard Paris, CHU Amiens-Picardie, Hôpital Avicenne AP-HP, Centre Eugène Marquis CRLCC, Centre Hospitalier Régional Universitaire de Besançon CHRU Besançon, Hôpital de la Timone CHU - APHM TIMONE, Service de Dermatologie et Allergologie CHRU Nancy, Hôpital Universitaire Carémeau Nîmes CHU Nîmes, Institut de Recherche en Cancérologie de Montpellier IRCM - U1194 Inserm - UM, CHU Pontchaillou Rennes, Centre hospitalier universitaire de Nantes CHU Nantes, Groupe de Recherche et d'Accueil en Droit et Economie de la Santé GRADES
مصطلحات موضوعية: Targeted therapy, Advanced melanoma, Cost-effectiveness analysis, Immunotherapy, Real-life clinical practice, Cost-Benefit Analysis, Cost-Effectiveness Analysis, France, Humans, Melanoma, Prospective Studies, Proto-Oncogene Proteins B-raf
الوصف: 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. A multistate model was developed to describe treatment sequences, associated costs, and health outcomes over 10 years. Sequences, clinical outcomes, utility scores, and economic data were extracted from the prospective Melbase cohort, collecting individual data in 1518 patients since 2013, from their AM diagnosis until their death. To adjust the differences in patients’ characteristics among sequences, weighting by inverse probability was used. In the BRAF-mutated population, the MONO-targeted therapies (TT)-anti-PD1 sequence was the less expensive, whereas the anti-PD1-BI-TT sequence had an incremental cost-effectiveness ratio (ICER) of 180,441 EUR/QALY. Regarding the BRAF wild-type population, the three sequences constituted the cost-effective frontier, with ICERs ranging from 116 to 806,000 EUR/QALY. For BRAF-mutated patients, the sequence anti-PD1-BI-TT appeared to be the most efficient one in BRAF-mutated AM patients until 2018. Regarding the BRAF wild-type population until 2018, the sequence starting with IPI+NIVO appeared inefficient compared to anti-PD1, considering the extra cost for the QALY gained. ; 29 ; 12
وصف الملف: application/octet-stream
العلاقة: CURRENT ONCOLOGY; http://hdl.handle.net/20.500.12210/80293Test
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4دورية أكاديمية
المؤلفون: Stratigos, Alexander J, Sekulic, Aleksandar, Peris, Ketty, Bechter, Oliver, Prey, Sorilla, Kaatz, Martin, Lewis, Karl D, Basset-Seguin, Nicole, Chang, Anne Lynn S, Dalle, Stèphane, Orland, Almudena Fernandez, Licitra, Lisa, Robert, Caroline, Ulrich, Claas, Hauschild, Axel, Migden, Michael R, Dummer, Reinhard, Li, Siyu, Yoo, Suk-Young, Mohan, Kosalai, Coates, Ebony, Jankovic, Vladimir, Fiaschi, Nathalie, Okoye, Emmanuel, Bassukas, Ioannis D, Loquai, Carmen, De Giorgi, Vincenzo, Eroglu, Zeynep, Gutzmer, Ralf, Ulrich, Jens, Puig, Susana, Seebach, Frank, Thurston, Gavin, Weinreich, David M, Yancopoulos, George D, Lowy, Israel, Bowler, Timothy, Fury, Matthew G
مصطلحات موضوعية: Adult, Aged, Anilides, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Basal Cell, Drug Resistance, Neoplasm, Female, Hedgehog Proteins, Humans, Immune Checkpoint Inhibitors, Male, Middle Aged, Neoplasm Recurrence, Local, Programmed Cell Death 1 Receptor, Pyridines, Skin Neoplasms
الوصف: Before February, 2021, there was no standard treatment regimen for locally advanced basal cell carcinoma after first-line hedgehog inhibitor (HHI) therapy. Cemiplimab, a PD-1 antibody, is approved for treatment of advanced cutaneous squamous cell carcinoma and has shown clinical activity as monotherapy in first-line non-small-cell lung cancer. Here, we present the primary analysis data of cemiplimab in patients with locally advanced basal cell carcinoma after HHI therapy. We did an open-label, multicentre, single-arm, phase 2 trial across 38 outpatient clinics, primarily at academic medical centres, in Canada, Europe, and the USA. Eligible patients (aged ≥18 years and with an Eastern Cooperative Oncology Group performance status of 0 or 1) with a histologically confirmed diagnosis of metastatic basal cell carcinoma (group 1) or locally advanced basal cell carcinoma (group 2) who had progressed on or were intolerant to previous HHI therapy were enrolled. Patients were not candidates for further HHI therapy due to progression of disease on or intolerance to previous HHI therapy or having no better than stable disease after 9 months on HHI therapy. Patients received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until progression or unacceptable toxicity. The primary endpoint was objective response by independent central review. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. The primary analysis is reported only for group 2; group 1 data have not reached maturity and will be reported when the timepoint, according to the statistical analysis plan, has been reached. This study is registered with ClinicalTrials.gov, NCT03132636, and is no longer recruiting new participants. Between Nov 16, 2017, and Jan 7, 2019, 84 patients were enrolled and treated with cemiplimab. At data cutoff on Feb 17, 2020, median duration of follow-up was 15 months (IQR 8-18). An objective response per independent central ...
العلاقة: http://hdl.handle.net/10668/17800Test; https://air.unimi.it/bitstream/2434/845195/2/Cemiplimab.pdfTest
الإتاحة: https://doi.org/10.1016/S1470-2045Test(21)00126-1
http://hdl.handle.net/10668/17800Test
https://air.unimi.it/bitstream/2434/845195/2/Cemiplimab.pdfTest -
5دورية أكاديمية
المؤلفون: Rousset, Perrine, Dalle, Stéphane, Mortier, Laurent, Dereure, Olivier, Dalac, Sophie, Dutriaux, Caroline, Leccia, Marie-Thérèse, Legoupil, Delphine, Brunet-Possenti, Florence, de Quatrebarbes, Julie, Grob, Jean-Jacques, Saiag, Philippe, Maubec, Eve, Stoebner, Pierre-Emmanuel, Granel-Brocard, Florence, Arnault, Jean-Philippe, Allayous, Clara, Oriano, Bastien, Lebbé, Celeste, Montaudié, Henri
المساهمون: Centre Hospitalier Universitaire de Nice CHU Nice, Centre Léon Bérard Lyon, Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 ONCO-THAI, Centre Hospitalier Régional Universitaire Lille CHRU Lille, Pathogenesis and Control of Chronic and Emerging Infections PCCEI, Service de Dermatologie (CHU de Dijon), CHU Bordeaux Bordeaux, Centre Hospitalier Universitaire Grenoble CHU, Centre Hospitalier Régional Universitaire de Brest CHRU Brest, AP-HP - Hôpital Bichat - Claude Bernard Paris, Centre Hospitalier Annecy-Genevois Saint-Julien-en-Genevois, Hôpital Ambroise Paré AP-HP, Université de Versailles Saint-Quentin-en-Yvelines UVSQ, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie BECCOH, Hôpital Avicenne AP-HP, Institut de Recherche en Cancérologie de Montpellier IRCM - U1194 Inserm - UM, Service de Dermatologie et Allergologie CHRU Nancy, CHU Amiens-Picardie, Immunologie humaine, physiopathologie & immunothérapie HIPI (UMR_S_976 / U976), Hopital Saint-Louis AP-HP AP-HP, Hôpital Hôtel-Dieu Paris, Service de Dermatologie Nice, Centre méditerranéen de médecine moléculaire C3M
مصطلحات موضوعية: Advanced melanoma, Adverse events, Chemotherapy, Immunotherapy, Melanoma of known primary, Melanoma of unknown primary, Survival, Systemic therapy, Targeted therapy, Humans, Neoplasms, Unknown Primary, Melanoma, Progression-Free Survival, Skin, Skin Neoplasms
الوصف: Background: 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. Co-primary outcomes were progression-free survival and overall survival. Secondary outcome was treatment-related toxicities. Multivariate and propensity score analyses were performed.Results: Of 1882 patients, 265 (14.1%) had advanced MUP. Patients with advanced MUP displayed more often unfavorable initial prognostic factors than those with cMKP. Progression-free and overall survival did not differ significantly between the groups (P = .73 and P = .93, respectively), as well as treatment-related toxicity rate and severity, regardless of treatment type.Limitations: No record of standard diagnostic criteria of MUP used in the participating centers.Conclusions: Although patients with MUP had less favorable baseline prognostic factors, they benefited from the novel therapies as much as those with cMKP. They should be managed according to similar strategies. ; 88 ; 4
العلاقة: Journal of the American Academy of Dermatology; http://hdl.handle.net/20.500.12210/80292Test
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6
المؤلفون: Lainé, Alexandra, Labiad, Ossama, Hernandez-Vargas, Hector, This, Sébastien, Sanlaville, Amélien, Léon, Sophie, Dalle, Stéphane, Sheppard, Dean, Travis, Mark A., Paidassi, Helena, Marie, Julien C.
المساهمون: Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Manchester [Manchester], Paidassi, Helena, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021)
Nature Communications
Nature Communications, 2021, 12, pp.6228. ⟨10.1038/s41467-021-26352-2⟩مصطلحات موضوعية: Cancer microenvironment, Male, Mice, Knockout, Integrins, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, T-Lymphocytes, Regulatory, Article, Mice, Inbred C57BL, Mice, Lymphocyte differentiation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Transforming Growth Factor beta, Neoplasms, Tumor Microenvironment, Tumour immunology, Animals, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Immunosuppression
الوصف: Presence of TGFβ in the tumor microenvironment is one of the most relevant cancer immune-escape mechanisms. TGFβ is secreted in an inactive form, and its activation within the tumor may depend on different cell types and mechanisms than its production. Here we show in mouse melanoma and breast cancer models that regulatory T (Treg) cells expressing the β8 chain of αvβ8 integrin (Itgβ8) are the main cell type in the tumors that activates TGFβ, produced by the cancer cells and stored in the tumor micro-environment. Itgβ8 ablation in Treg cells impairs TGFβ signalling in intra-tumoral T lymphocytes but not in the tumor draining lymph nodes. Successively, the effector function of tumor infiltrating CD8+ T lymphocytes strengthens, leading to efficient control of tumor growth. In cancer patients, anti-Itgβ8 antibody treatment elicits similar improved cytotoxic T cell activation. Thus, this study reveals that Treg cells work in concert with cancer cells to produce bioactive-TGFβ and to create an immunosuppressive micro-environment.
TGFβ is secreted in an inactive form in the tumor microenvironment. Authors here show that although TGFβ is produced mainly by cancer cells, regulatory T cells are necessary for its activation via expression of the b8 chain of avb8 integrin. Thus, both cell types contribute to TGFβ dependent tumor growth.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::7674595bee38c19e699cedf83e4a394fTest
https://doaj.org/article/0099bf33b303405fa97900689fb2a35eTest -
7
المؤلفون: Mangin, Marie‐Alix, Boespflug, Amélie, Maucort Boulch, Delphine, Vacheron, Charles‐Hervé, Carpentier, Isabelle, Thomas, Luc, Dalle, Stéphane
المصدر: Cancer Medicine, Vol 10, Iss 10, Pp 3155-3164 (2021)
Cancer Medicineمصطلحات موضوعية: Male, nivolumab, Clinical Cancer Research, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, targeted therapy, Progression-Free Survival, cytotoxic chemotherapy, Antineoplastic Combined Chemotherapy Protocols, melanoma, Humans, Female, immunotherapy, pembrolizumab, Immune Checkpoint Inhibitors, Protein Kinase Inhibitors, RC254-282, Original Research, Aged, Retrospective Studies
الوصف: Background Cytotoxic chemotherapy (CC) is currently used in metastatic melanoma after patients have developed resistance to immune checkpoint inhibitors (ICI) and/or Mitogen‐Activated Protein Kinase inhibitors (MAPKi). We sought to evaluate if a previous treatment by ICI or MAPKi influences clinical outcomes in patients treated by CC in metastatic melanoma. Methods Eighty‐eight patients with a metastatic melanoma, treated by CC after a previous treatment by ICI or MAPKi between January 2009 and October 2019, were retrospectively analyzed. Progression‐Free‐Survival (PFS), Overall Survival (OS), Overall Response Rate (ORR), and Disease Control Rate (DCR) were evaluated in patients treated by CC according to their prior treatment by ICI or MAPKi. Results Patients treated by CC after ICI tended to have a better median PFS (2.81 months (2.39–5.30) versus 2.40 months (0.91–2.75), p = 0.023), median OS (6.03 months (3.54–11.54) versus 4.44 months (1.54–8.59), p = 0.27), DCR (26.0% vs. 10.5%, p = 0.121) and ORR (22.0% vs. 7.9% p = 0.134) than those previously treated by MAPKi. Conclusions A prior treatment by an MAPKi may be associated with a worse response to CC than ICI, and further investigations should be performed to confirm if there is a clinical benefit to propose CC in this setting.
Cytotoxic chemotherapy may be used as a last resort after failure of a prior treatment by targeted therapy or immunotherapy in metastatic melanoma. The aim of this study was to evaluate if a prior treatment by targeted therapy or immunotherapy may influence clinical outcomes in patients treated by a second line cytotoxic chemotherapy in metastatic melanoma. We found that patients treated by cytotoxic chemotherapy after prior treatment by targeted therapy, tended to have worse clinical outcomes than patients previously treated by immunotherapy and that prior immunotherapy does not seem to potentiate response to cytotoxic chemotherapy when compared to historical cohorts.الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::5e4b7b286b5b8ea479c3cc8412c00cfdTest
https://doaj.org/article/0ab964971a5348f598cbc837ed78ca3dTest -
8دورية أكاديمية
المؤلفون: Larkin, James, Weber, Jeffrey, Del Vecchio, Michele, Gogas, Helen, Arance, Ana M, Dalle, Stephane, Cowey, C Lance, Schenker, Michael, Grob, Jean-Jacques, Chiarion-Sileni, Vanna, Márquez-Rodas, Iván, Butler, Marcus O, Di Giacomo, Anna Marie, Middleton, Mark R, De la Cruz-Merino, Luis, Arenberger, Petr, Atkinson, Victoria, Hill, Andrew, Fecher, Leslie A, Millward, Michael, Khushalani, Nikhil I, Queirolo, Paola, Long, Georgina V, Lobo, Maurice, Askelson, Margarita, Ascierto, Paolo A, Mandalá, Mario
مصطلحات موضوعية: AJCC-8 criteria, Distant metastases, Ipilimumab, Melanoma adjuvant therapy, Nivolumab, Recurrence-free survival, Stage 3, Adjuvants, Immunologic, Humans, Melanoma, Neoplasm Staging, Skin Neoplasms
الوصف: Nivolumab was approved as adjuvant therapy for melanoma based on data from CheckMate 238, which enrolled patients per American Joint Committee on Cancer version 7 (AJCC-7) criteria. Here, we analyse long-term outcomes per AJCC-8 staging criteria compared with AJCC-7 results to inform clinical decisions for patients diagnosed per AJCC-8. In a double-blind, phase 3 trial (NCT02388906), patients aged ≥15 years with resected, histologically confirmed AJCC-7 stage IIIB, IIIC, or IV melanoma were randomised to receive nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses and then every 12 weeks, both intravenously ≤1 year. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were assessed in patients with stage III disease, per AJCC-7 and AJCC-8. Per AJCC-7 staging, 42.4% and 57.3% of patients were in substage IIIB and IIIC, respectively; per AJCC-8, 1.1%, 30.4%, 62.8%, and 5.0% were in IIIA, IIIB, IIIC, and IIID. After 4 years' minimum follow-up, the AJCC-7 superior efficacy of nivolumab over ipilimumab in patients with resected stage III melanoma was preserved per AJCC-8 analysis. No statistically significant difference in RFS between stage III substage hazard ratios was observed per AJCC-7 or -8 staging criteria (interaction test: AJCC-7, P = 0.8115; AJCC-8, P = 0.1051; P = 0.8392 ((AJCC-7) and P = 0.8678 (AJCC-8) for DMFS). CheckMate 238 4-year RFS and DMFS outcomes are consistent per AJCC-7 and AJCC-8 staging criteria. Outcome benefits can therefore be translated for patients diagnosed per AJCC-8.
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9دورية أكاديمية
المؤلفون: Bottomley, Andrew, Coens, Corneel, Mierzynska, Justyna, Blank, Christian U, Mandalà, Mario, Long, Georgina V, Atkinson, Victoria G, Dalle, Stéphane, Haydon, Andrew M, Meshcheryakov, Andrey, Khattak, Adnan, Carlino, Matteo S, Sandhu, Shahneen, Puig, Susana, Ascierto, Paolo A, Larkin, James, Lorigan, Paul C, Rutkowski, Piotr, Schadendorf, Dirk, Koornstra, Rutger, Hernandez-Aya, Leonel, Di Giacomo, Anna Maria, van den Eertwegh, Alfonsus J M, Grob, Jean-Jacques, Gutzmer, Ralf, Jamal, Rahima, van Akkooi, Alexander C J, Krepler, Clemens, Ibrahim, Nageatte, Marreaud, Sandrine, Kicinski, Michal, Suciu, Stefan, Robert, Caroline, Eggermont, Alexander M M, EORTC Melanoma Group
المساهمون: Boehncke, Wolf-Henning
المصدر: ISSN: 1470-2045 ; Lancet. Oncology, vol. 22, no. 5 (2021) p. 655-664.
مصطلحات موضوعية: info:eu-repo/classification/ddc/616, Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized / therapeutic use, Double-Blind Method, Female, Humans, Male, Melanoma / drug therapy, Melanoma / mortality, Melanoma / pathology, Melanoma / psychology, Middle Aged, Neoplasm Staging, Quality of Life, Skin Neoplasms / drug therapy, Skin Neoplasms / mortality, Skin Neoplasms / pathology, Skin Neoplasms / psychology
الوصف: Background : The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43-0·74]; p<0·0001). This study reports the results from the health-related quality-of-life (HRQOL) exploratory endpoint. Methods : This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries. Patients aged 18 years or older with previously untreated histologically confirmed stage IIIA, IIIB, or IIIC resected cutaneous melanoma, and an Eastern Cooperative Oncology Group performance status score of 1 or 0 were eligible. Patients were randomly assigned (1:1) using a central interactive voice-response system on the basis of a minimisation technique stratified for stage and geographic region to receive intravenously 200 mg pembrolizumab or placebo. Treatment was administered every 3 weeks for 1 year, or until disease recurrence, unacceptable toxicity, or death. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, with global health/quality of life (GHQ) over 2 years measured by the EORTC QLQ-C30 as the primary analysis. Analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37, and long-term follow-up is ongoing. Findings : Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to pembrolizumab (n=514) or placebo (n=505). Median follow-up was 15·1 months (IQR 12·8-16·9) at the time of this analysis. HRQOL compliance was greater than 90% at baseline, greater than 70% during the first year, and greater than 60% thereafter for both groups. Because of low absolute compliance numbers at later follow-up, the analysis was truncated to week 84. Baseline GHQ scores were similar ...
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33857414; info:eu-repo/semantics/dataset/url/https://clinicaltrials.gov/ct2/show/results/NCT02362594Test; https://archive-ouverte.unige.ch/unige:159804Test; unige:159804
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10دورية أكاديمية
المؤلفون: Dalle, Stéphane, Mortier, Laurent, Corrie, Pippa, Lotem, Michal, Board, Ruth, Arance, Ana María, Meiss, Frank, Terheyden, Patrick, Gutzmer, Ralf, Buysse, Brian, Oh, Kelly, Brokaw, Jane, Le, T Kim, Mathias, Susan D, Scotto, Julie, Lord-Bessen, Jennifer, Moshyk, Andriy, Kotapati, Srividya, Middleton, Mark R
مصطلحات موضوعية: Advanced melanoma, Ipilimumab, Overall survival, Quality of life, Real-world, Subsequent therapy, Adult, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Chemoradiotherapy, Female, Follow-Up Studies, Humans, Immune Checkpoint Inhibitors, Male, Melanoma, Middle Aged, Prospective Studies, Radiosurgery, Skin Neoplasms, Survival Analysis, Treatment Outcome, Young Adult
الوصف: Funder: This work was supported by Bristol Myers Squibb (no grant number is applicable). ; BACKGROUND: Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. METHODS: IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. RESULTS: Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti-programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab-treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab-treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy ...
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الإتاحة: https://doi.org/10.17863/CAM.70643Test
https://www.repository.cam.ac.uk/handle/1810/323189Test
