المؤلفون: Stéphane Champiat, Christophe Massard, Anne-Laure Voisin, Capucine Baldini, Benjamin Besse, Cedric Pobel, Vincent Thomas de Montpréville, Laurence Albiges, Christina Mateus, Jérôme Le Pavec, Samy Ammari, Aurélien Marabelle, Noémie Chanson, Patricia Pautier, Jean-Marie Michot, Patricia Romano-Martin, Charlotte Cabanié, François-Xavier Danlos, Caroline Even, Olivier Lambotte, Sophie Hans, Emilie Routier, A. Laparra, Celine Boutros, Corinne Balleyguier, Romain David Seban, Samuel Dolidon, Caroline Robert

المصدر: European Journal of Cancer. 156:46-59

مصطلحات موضوعية: Adult, Male, Cancer Research, medicine.medical_specialty, Time Factors, Sarcoidosis, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Risk Assessment, Severity of Illness Index, Asymptomatic, Young Adult, Risk Factors, Neoplasms, Internal medicine, Humans, Medicine, CTLA-4 Antigen, Registries, Adverse effect, Immune Checkpoint Inhibitors, Aged, Retrospective Studies, Aged, 80 and over, Granuloma, business.industry, Melanoma, Case-control study, Cancer, Immunotherapy, Middle Aged, medicine.disease, Treatment Outcome, Oncology, Cohort, Female, medicine.symptom, Tomography, X-Ray Computed, business

الوصف: Sarcoid-like granulomatosis (SLG) reaction caused by immunotherapy remains poorly understood. This study aims to investigate the outcome of patients with cancer and SLG associated with immunotherapy.Between April 2016 and June 2020, 434 patients with immunological adverse events were screened from the ImmunoTOX assessment board of Gustave Roussy, an academic cancer centre in France. Among them, 28 patients had SLG associated with immunotherapy (SLG cohort) and 406 patients had other immunological adverse events (control cohort). Clinical characteristics and outcome of patients were compared from SLG and control cohort.The SLG cohort consisted of 28 patients, 14 women and 14 men, with the median (range) age of 56.5 (28.7-75.3) years. Patients in the SLG cohort with sarcoidosis were asymptomatic (only radiographical finding) in 13 (46.4%) cases; otherwise, the most frequent symptoms were dyspnoea in 8 (28.6%) patients and cough in 5 (17.8%) patients. The computerised tomography scan found sarcoidosis localisations in mediastinal or peri-hilar thoracic lymph nodes in 26 (92.9%) patients, and lung parenchymal involvement was found in 14 (50.0%) patients. The radiographic Scadding stages for sarcoidosis classification were distributed in stages 0, I, II, III and IV in 2 patients (7.1%), 13 patients (46.4%), 11 patients (39.3%), 1 patient (3.6%) and 1 patient (3.6%), respectively. Compared with patients with other immunological toxicities (cohort control), patients with sarcoidosis presented most frequently with melanoma (75.0% versus 21.9% of patients; p 0.001) and more often received combined therapies of anti-programmed cell death 1 plus anti-cytotoxic T-lymphocyte antigen 4 protein (46.4% versus 12.6% of patients; p = 0.002). Patients with sarcoidosis had an improved overall survival (OS); the median OS was not reached in the SLG cohort and 40.4 months in the control cohort, hazard ratio = 0.232 (95% confidence interval: 0.086-0.630) (p = 0.002).Sarcoidosis-like reactions in patients receiving immunotherapy were reported as non-severe immunological reactions in most cases and were correlated with improved OS. SLG should not be misdiagnosed as tumour progression in patients receiving immunotherapy treatment for cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efdee7d15d010644e44ad37349b1f08bTest
https://doi.org/10.1016/j.ejca.2021.07.015Test

المؤلفون: Reinhard Dummer, Georgina V. Long, Caroline Robert, Hussein A. Tawbi, Keith T. Flaherty, Paolo A. Ascierto, Paul D. Nathan, Piotr Rutkowski, Oleg Leonov, Caroline Dutriaux, Mario Mandalà, Paul Lorigan, Pier Francesco Ferrucci, Jean Jacques Grob, Nicolas Meyer, Helen Gogas, Daniil Stroyakovskiy, Ana Arance, Jan C. Brase, Steven Green, Tomas Haas, Aisha Masood, Eduard Gasal, Antoni Ribas, Dirk Schadendorf

المساهمون: University of Zurich

المصدر: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 40, iss 13
Dummer, R, Long, G V, Robert, C, Tawbi, H A, Flaherty, K T, Ascierto, P A, Nathan, P D, Rutkowski, P, Leonov, O, Dutriaux, C, Mandalà, M, Lorigan, P, Ferrucci, P F, Grob, J J, Meyer, N, Gogas, H, Stroyakovskiy, D, Arance, A, Brase, J C, Green, S, Haas, T, Masood, A, Gasal, E, Ribas, A & Schadendorf, D 2022, ' Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma ', Journal of clinical oncology : official journal of the American Society of Clinical Oncology . https://doi.org/10.1200/JCO.21.01601Test

مصطلحات موضوعية: Proto-Oncogene Proteins B-raf, Adult, Cancer Research, Skin Neoplasms, Adolescent, Pyridones, Clinical Trials and Supportive Activities, Clinical Sciences, Oncology and Carcinogenesis, Medizin, 610 Medicine & health, Pyrimidinones, Antibodies, Death Domain, Clinical Research, Neoplasms, Oximes, Antineoplastic Combined Chemotherapy Protocols, Receptors, Monoclonal, Genetics, Humans, Oncology & Carcinogenesis, Melanoma, Humanized, Cancer, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Human Genome, Imidazoles, Evaluation of treatments and therapeutic interventions, 10177 Dermatology Clinic, Second Primary, Oncology, 6.1 Pharmaceuticals, Mutation

الوصف: PURPOSEPreclinical data suggest the combination of an anti–programmed death receptor 1 antibody plus dabrafenib and trametinib to have superior antitumor activity compared with dabrafenib plus trametinib alone. These observations are supported by translational evidence suggesting that immune checkpoint inhibitors plus targeted therapy may improve treatment outcomes in patients with BRAF V600–mutant metastatic melanoma. COMBI-i is a phase III trial evaluating spartalizumab, an anti–programmed death receptor 1 antibody, in combination with dabrafenib and trametinib (sparta-DabTram), versus placebo plus dabrafenib and trametinib (placebo-DabTram) in patients with BRAF V600–mutant unresectable or metastatic melanoma.METHODSPatients received spartalizumab 400 mg intravenously every 4 weeks plus dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily or placebo-DabTram. Participants were age ≥ 18 years with unresectable or metastatic BRAF V600–mutant melanoma. The primary end point was investigator-assessed progression-free survival. Overall survival was a key secondary end point (ClinicalTrials.gov identifier: NCT02967692 ).RESULTSAt data cutoff (July 1, 2020), the median progression-free survival was 16.2 months (95% CI, 12.7 to 23.9 months) in the sparta-DabTram arm versus 12.0 months (95% CI, 10.2 to 15.4 months) in the placebo-DabTram arm (hazard ratio, 0.82 [95% CI, 0.66 to 1.03]; P = .042 [one-sided; nonsignificant]). The objective response rates were 69% (183 of 267 patients) versus 64% (170 of 265 patients), respectively. Grade ≥ 3 treatment-related adverse events occurred in 55% (146 of 267) of patients in the sparta-DabTram arm and 33% (88 of 264) in the placebo-DabTram arm.CONCLUSIONThe study did not meet its primary end point; broad first-line use of sparta-DabTram is not supported by these results. Further biomarker-driven investigation may identify patient subpopulations who could benefit from checkpoint inhibitor plus targeted therapy combinations.

وصف الملف: 928_Dummer_R._et_al._Randomized_Phase_III_Trial_Evaluationg_Spartalizumab_plus_Dabrafenib_and_Trametinib_for_BRAF_V600_mutant_JCO_2022.pdf - application/pdf; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::512e67c5f66bacf61087d7e838e0dc59Test
https://www.zora.uzh.ch/id/eprint/213526Test/

المؤلفون: Félix Pham, Amélie Boespflug, Gérard Duru, Alice Phan, Nicolas Poulalhon, Laura Weiler, Masaru Tanaka, Aimilios Lallas, Dai Ogata, Anne Céline Davaine, Philippe Bahadoran, Xavier Balguerie, Grażyna Kamińska-Winciorek, Isabelle Tromme, Osvaldo Correia, Moon-Bum Kim, Ashfaq A. Marghoob, null Linda Martin, Pascale Guitera, Mariame Meziane, Juliette Miquel, Je-Ho Mun, Giuseppe Argenziano, Didier Bessis, Johnny Bourke, Zeljko Mijuskovic, Christine Chiaverini, Cloé Corven-Benoit, Catherine Droitcourt, François Skowron, Myriam Marque, Iris Zalaudek, Cliff Rosendahl, David Moreno-Ramirez, Pierre Vabres, Holger Haenssle, Josep Malvehy, Susana Puig, Caroline Robert, Thomas R. Schopf, Alon Scope, Stéphane Dalle, Luc Thomas

المساهمون: UCL - SSS/IRSS - Institut de recherche santé et société, UCL - (SLuc) Service de dermatologie, Pham, Félix, Boespflug, Amélie, Duru, Gérard, Phan, Alice, Poulalhon, Nicola, Weiler, Laura, Tanaka, Masaru, Lallas, Aimilio, Ogata, Dai, Davaine, Anne Céline, Bahadoran, Philippe, Balguerie, Xavier, Kamińska-Winciorek, Grażyna, Tromme, Isabelle, Correia, Osvaldo, Kim, Moon-Bum, Marghoob, Ashfaq A, Linda Martin, Null, Guitera, Pascale, Meziane, Mariame, Miquel, Juliette, Mun, Je-Ho, Argenziano, Giuseppe, Bessis, Didier, Bourke, Johnny, Mijuskovic, Zeljko, Chiaverini, Christine, Corven-Benoit, Cloé, Droitcourt, Catherine, Skowron, Françoi, Marque, Myriam, Zalaudek, Iri, Rosendahl, Cliff, Moreno-Ramirez, David, Vabres, Pierre, Haenssle, Holger, Malvehy, Josep, Puig, Susana, Robert, Caroline, Schopf, Thomas R, Scope, Alon, Dalle, Stéphane, Thomas, Luc, Pham, F., Boespflug, A., Duru, G., Phan, A., Poulalhon, N., Weiler, L., Tanaka, M., Lallas, A., Ogata, D., Davaine, A. C., Bahadoran, P., Balguerie, X., Kaminska-Winciorek, G., Tromme, I., Correia, O., Kim, M. -B., Marghoob, A. A., Linda, Martin, Guitera, P., Meziane, M., Miquel, J., Mun, J. -H., Argenziano, G., Bessis, D., Bourke, J., Mijuskovic, Z., Chiaverini, C., Corven-Benoit, C., Droitcourt, C., Skowron, F., Marque, M., Zalaudek, I., Rosendahl, C., Moreno-Ramirez, D., Vabres, P., Haenssle, H., Malvehy, J., Puig, S., Robert, C., Schopf, T. R., Scope, A., Dalle, S., Thomas, L.

المصدر: Journal of the American Academy of Dermatology, p. [1-8] (2022)

مصطلحات موضوعية: Adult, Subungual melanoma, Skin Neoplasms, nevus of the nail unit, Dermoscopy, dermatoscopy, Dermatology, congenital nail matrix nevu, Longitudinal melanonychia, Melanonychia striata, Diagnosis, Differential, Nail Diseases, Congenital, children, Dermatoscopy, Humans, Prospective Studies, Child, Melanoma, Nevus, Children, melanonychia striata, Pediatric, congenital, congenital nail matrix nevus, longitudinal melanonychia, pediatric, subungual melanoma, Infant, Newborn, Congenital nail matrix nevus, Nevus of the nail unit, Child, Preschool

الوصف: Background: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. Objective: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). Methods: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. Results: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar (“brush-like”) pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. Limitations: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. Conclusion: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar (“brush-like”) pattern is a suggestive feature of congenital and congenital-type NMN.

وصف الملف: STAMPA

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21428c7685daa49d2aa23a8fd46688a4Test
https://hdl.handle.net/2078.1/259595Test

المؤلفون: Ramon Arntz, Serena Martelli, R. Gutzmer, Nicholas Squittieri, Dirk Schadendorf, Caroline Robert, Carmen Loquai, Reinhard Dummer

المساهمون: University of Zurich, Gutzmer, Ralf

المصدر: BMC Cancer, Vol 21, Iss 1, Pp 1-9 (2021)
BMC Cancer

مصطلحات موضوعية: Adult, Cancer Research, Skin Neoplasms, Pyridines, medicine.medical_treatment, Medizin, Tumor outcome, Vismodegib, 610 Medicine & health, mRECIST, Drug Administration Schedule, Hedgehog pathway inhibitor, Sonidegib, chemistry.chemical_compound, Double-Blind Method, 1311 Genetics, Confidence Intervals, Genetics, Humans, Medicine, Anilides, Basal cell carcinoma, 1306 Cancer Research, Response Evaluation Criteria in Solid Tumors, RC254-282, medicine.diagnostic_test, business.industry, Research, Biphenyl Compounds, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 10177 Dermatology Clinic, Magnetic resonance imaging, medicine.disease, Confidence interval, Radiation therapy, Treatment Outcome, chemistry, Oncology, Carcinoma, Basal Cell, Disease Progression, 2730 Oncology, business, Nuclear medicine, Progressive disease, medicine.drug

الوصف: Background The BOLT study for sonidegib, a Hedgehog pathway inhibitor (HHI) approved for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy, used modified Response Evaluation Criteria in Solid Tumors (mRECIST) for laBCC tumor evaluation. The ERIVANCE study for vismodegib, another HHI, used a composite RECIST endpoint of ≥30% reduction in externally visible tumor or radiographic dimension, or complete ulceration resolution. This preplanned sensitivity BOLT analysis evaluated efficacy outcomes using ERIVANCE-like criteria in patients with laBCC who received sonidegib 200 mg once daily. Methods This phase 2, double-blind study randomized patients 1:2 to sonidegib 200:800 mg daily, respectively. Key endpoints included objective response rate (ORR), duration of response (DOR), complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). laBCC tumors were assessed by both mRECIST and ERIVANCE-like criteria. Per mRECIST, an overall response of CR was based on negative histology; photographic assessment of CR, PR (scar/fibrosis only), SD (scar/fibrosis only), or not available (NA); and a magnetic resonance imaging response of CR or NA. An overall response of CR was primarily based on negative histology using ERIVANCE-like criteria. Results Per mRECIST criteria, ORR (95% confidence interval [CI]) by central and investigator review for patients with laBCC (n = 66) was 56.1% (43.3–68.3%) and 71.2% (58.7–81.7%), respectively. CR per central review was achieved in 3 (4.5%) patients and PR, SD, and PD occurred in 34 (51.5%), 23 (34.8%), and 1 (1.5%) patient, respectively. Median (95% CI) DOR was 26.1 months (not estimable [NE]). Using ERIVANCE-like criteria, efficacy outcomes per central and investigator review were higher, with an ORR (95% CI) of 60.6% (47.8–72.4%) and 74.2% (62.0–84.2%), respectively. CR per central review was reached in 14 (21.2%) patients and PR, SD, and PD occurred in 26 (39.4%), 20 (30.3%), and 1 (1.5%) patient, respectively. DOR was unchanged with a median (95% CI) of 26.1 months (NE). Conclusions Overall, applying ERIVANCE-like criteria to patients with laBCC receiving sonidegib 200 mg daily yielded higher response rates vs mRECIST criteria. Trial registration BOLT registration: ClinicalTrials.gov (NCT01327053) on March 30, 2011.

وصف الملف: 924_Gutzmer_R._et_al._Assessment_of_various_efficacy_outcomes_using_ERIVANCE-like_criteria_in_patients_with_locally_advanced_basal_cell_carcinoma_receiving_sonidegib_BMC_Cancer_2021.pdf - application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db8d273e34be76c08b02bf466b6db805Test
https://doi.org/10.5167/uzh-210585Test

المؤلفون: Christian U. Blank, Stéphane Dalle, Alexander M.M. Eggermont, Sandrine Marreaud, Matteo S. Carlino, Alfonsus J. M. van den Eertwegh, Stefan Suciu, Nageatte Ibrahim, Rahima Jamal, Paolo A. Ascierto, Alexander C.J. van Akkooi, Michal Kicinski, Piotr Rutkowski, Georgina V. Long, Dirk Schadendorf, Ralf Gutzmer, Shahneen Sandhu, Andrew Haydon, Victoria Atkinson, Susana Puig, Adnan Khattak, Anna Maria Di Giacomo, Clemens Krepler, Mario Mandalà, Rutger H. T. Koornstra, Caroline Robert, Jean-Jacques Grob, Leonel Hernandez-Aya, Paul Lorigan, James Larkin

المساهمون: Medical oncology, CCA - Cancer Treatment and quality of life, AII - Cancer immunology

المصدر: Jama Oncology, 6, 519-527
Eggermont, A M M, Kicinski, M, Blank, C U, Mandala, M, Long, G V, Atkinson, V, Dalle, S, Haydon, A, Khattak, A, Carlino, M S, Sandhu, S, Larkin, J, Puig, S, Ascierto, P A, Rutkowski, P, Schadendorf, D, Koornstra, R, Hernandez-Aya, L, di Giacomo, A M, van den Eertwegh, A J M, Grob, J-J, Gutzmer, R, Jamal, R, Lorigan, P C, Krepler, C, Ibrahim, N, Marreaud, S, van Akkooi, A, Robert, C & Suciu, S 2020, ' Association between Immune-Related Adverse Events and Recurrence-Free Survival among Patients with Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo: A Secondary Analysis of a Randomized Clinical Trial ', JAMA Oncology, vol. 6, no. 4, pp. 519-527 . https://doi.org/10.1001/jamaoncol.2019.5570Test
Eggermont, A M M, Kicinski, M, Blank, C U, Mandala, M, Long, G V, Atkinson, V, Dalle, S, Haydon, A, Khattak, A, Carlino, M S, Sandhu, S, Larkin, J, Puig, S, Ascierto, P A, Rutkowski, P, Schadendorf, D, Koornstra, R, Hernandez-Aya, L, Di Giacomo, A M, van den Eertwegh, A J M, Grob, J-J, Gutzmer, R, Jamal, R, Lorigan, P C, Krepler, C, Ibrahim, N, Marreaud, S, van Akkooi, A, Robert, C & Suciu, S 2020, ' Association Between Immune-Related Adverse Events and Recurrence-Free Survival Among Patients With Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo : A Secondary Analysis of a Randomized Clinical Trial ', JAMA oncology . https://doi.org/10.1001/jamaoncol.2019.5570Test
Jama Oncology, 6, 4, pp. 519-527
JAMA Oncology, 6(4), 519-527. American Medical Association

مصطلحات موضوعية: Adult, Male, Cancer Research, medicine.medical_specialty, Population, Medizin, Pembrolizumab, Placebo, Antibodies, Monoclonal, Humanized, Disease-Free Survival, law.invention, Placebos, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Medicine, Humans, 030212 general & internal medicine, education, Adverse effect, Melanoma, Aged, Neoplasm Staging, Proportional Hazards Models, education.field_of_study, Manchester Cancer Research Centre, business.industry, Proportional hazards model, ResearchInstitutes_Networks_Beacons/mcrc, Hazard ratio, Middle Aged, Ipilimumab, Clinical trial, Oncology, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business

الوصف: Importance: Whether immune-related adverse events (irAEs) indicate drug activity in patients treated with immune checkpoint inhibitors remains unknown.Objective: To investigate the association between irAEs and recurrence-free survival (RFS) in the double-blind EORTC 1325/KEYNOTE-054 clinical trial comparing pembrolizumab therapy and placebo for the treatment of patients with high-risk stage III melanoma.Design, Setting, and Participants: A total of 1019 adults with stage III melanoma were randomly assigned on a 1:1 ratio to receive treatment with pembrolizumab therapy or placebo. Eligible patients were adults 18 years and older with complete resection of cutaneous melanoma metastatic to lymph nodes, classified with stage IIIA (at least 1 micrometastasis measuring >1 mm in greatest diameter), IIIB, or IIIC (without in-transit metastasis) cancer. Patients were randomized from August 26, 2015, to November 14, 2016. The clinical cutoff for the data set was October 2, 2017. Analyses were then performed on the database, which was locked on November 28, 2017.Interventions: Participants were scheduled to receive 200 mg of pembrolizumab or placebo every 3 weeks for a total of 18 doses for approximately 1 year or until disease recurrence, unacceptable toxic effects, major protocol violation, or withdrawal of consent.Main Outcomes and Measures: The association between irAEs and RFS was estimated using a Cox model adjusted for sex, age, and AJCC-7 stage, with a time-varying covariate that had a value of 0 before irAE onset and 1 after irAE onset.Results: Of 1011 patients who began treatment with pembrolizumab therapy or placebo, 622 (61.5%) were men and 389 (38.5%) were women; 386 patients (38.2%) were aged 50 to 64 years, 377 (37.3%) were younger than 50 years, and 248 (24.5%) were 65 years and older. Consistent with the reported main analysis in the intent-to-treat population, RFS was longer in the pembrolizumab arm compared with the placebo arm (hazard ratio [HR], 0.56; 98.4% CI, 0.43-0.74) among patients who started treatment. The incidence of irAEs was 190 (37.4%) in the pembrolizumab arm (n = 509) and 45 (9.0%) in the placebo arm (n = 502); in each treatment group, the incidence was similar for men and women. The occurrence of an irAE was associated with a longer RFS in the pembrolizumab arm (HR, 0.61; 95% CI, 0.39-0.95; P = .03) in both men and women. However, in the placebo arm, this association was not significant. Compared with the placebo arm, the reduction in the hazard of recurrence or death in the pembrolizumab arm was greater after the onset of an irAE than without or before an irAE (HR, 0.37; 95% CI, 0.24-0.57 vs HR, 0.61; 95% CI, 0.49-0.77, respectively; P = .03).Conclusions and Relevance: In this study, the occurrence of an irAE was associated with a longer RFS in the pembrolizumab arm.Trial Registrations: ClinicalTrials.gov identifier: NCT02362594; EudraCT identifier: 2014-004944-37.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9b431bc34ae329792ac7bd923376806Test
https://hdl.handle.net/2066/218502Test

المؤلفون: Piotr Rutkowski, Sama Ahsan, Jean-Jacques Grob, Matteo S. Carlino, James R. Anderson, Merrick I. Ross, John M. Kirkwood, Jeffrey E. Gershenwald, Caroline Robert, Jason J. Luke, Nageatte Ibrahim, Charles H. Yoon, Peter Mohr, Georgina V. Long, Alexander M.M. Eggermont, Axel Hauschild, Paolo A. Ascierto, Andrew Poklepovic, Richard A. Scolyer

المصدر: Future Oncology. 16:4429-4438

مصطلحات موضوعية: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Skin Neoplasms, Adolescent, medicine.medical_treatment, Dermatologic Surgical Procedures, Programmed Cell Death 1 Receptor, Pembrolizumab, Antibodies, Monoclonal, Humanized, Placebo, Disease-Free Survival, Placebos, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Internal medicine, medicine, Adjuvant therapy, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, Young adult, Child, Melanoma, Neoplasm Staging, Randomized Controlled Trials as Topic, Cross-Over Studies, business.industry, General Medicine, medicine.disease, Crossover study, Clinical trial, Clinical Trials, Phase III as Topic, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, Adjuvant

الوصف: Patients with high-risk stage II melanoma are at significant risk for recurrence after surgical resection. Adjuvant treatment options to lower the risk for distant metastases are limited. Although adjuvant IFN-α2b is associated with improved relapse-free survival in patients with high-risk melanoma, toxicity and limited overall survival benefits limit its use. Adjuvant treatment with the PD-1 inhibitor pembrolizumab significantly improved recurrence-free survival, compared with placebo, in patients with resected stage III melanoma in the Phase III KEYNOTE-054 trial; efficacy in patients with stage II disease has not been established. This article describes the design and rationale of KEYNOTE-716 (NCT03553836), a two-part, randomized, placebo-controlled, multicenter Phase III study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Clinical trial registry & ID: ClinicalTrials.gov, NCT03553836

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6a00dd1a28f82ed3c8216b416ba2d53Test
https://doi.org/10.2217/fon-2019-0666Test

المؤلفون: Antoine Moya-Plana, David Mangin, Laurent Dercle, Rabah Taouachi, Odile Casiraghi, Samy Ammari, France Nguyen, Stéphane Temam, Caroline Robert, Philippe Gorphe

المصدر: Oral Oncology. 97:44-49

مصطلحات موضوعية: Adult, Male, Nasal cavity, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, medicine, Overall survival, Humans, 030223 otorhinolaryngology, Head and neck, Surgical treatment, Melanoma, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Mucous Membrane, business.industry, Mucosal melanoma, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Radiation therapy, medicine.anatomical_structure, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Cohort, Female, Radiology, Nasal Cavity, Oral Surgery, business, Paranasal Sinus Neoplasms

الوصف: Background Head and neck mucosal melanoma (HNMM) is a rare and aggressive disease with a high metastatic potential. Two staging systems are currently available: one specific to HNMM (mmTNM) and one specific to primary tumour sites (sccTNM). Our main objective was to assess the prognostic value of both of these classifications in order to allow accurate risk-based classification. Methods We performed a retrospective cohort study of patients with HNMM treated consecutively between 2000 and 2017. All of the patients were restaged using the mmTNM and the sccTNM. A prognostic analysis was carried out according to both staging systems. Results There were 96 patients with an HNMM in our cohort, of whom 80 underwent surgical treatment followed by radiotherapy. The median overall survival (OS) and progression-free survival (PFS) for the operated patients were 39 months (95% CI, 21.6–56.4 months) and 18 months (95% CI, 6.5–29.5 months), respectively. A paranasal sinus localization was associated with lower survival compared to a nasal cavity primary localization (p Conclusions Both of the classifications should be combined, in order to improve the risk-stratification of patients with HNMM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::090bcc864b274b589d6a74bf06288162Test
https://doi.org/10.1016/j.oraloncology.2019.07.026Test

المؤلفون: Fareeda Hosein, Veerle de Pril, Jon M. Richards, Jean-Jacques Grob, Vanna Chiarion-Sileni, Henrik Schmidt, Virginia Ferraresi, Alessandro Testori, Omid Hamid, Jeffrey S. Weber, Jedd D. Wolchok, Alexander M.M. Eggermont, Paolo A. Ascierto, Stefan Suciu, Caroline Robert, Michael Smylie, Reinhard Dummer, Michal Kicinski, Céleste Lebbé, Michele Maio

المساهمون: University of Zurich, Eggermont, Alexander M M

المصدر: Eggermont, A M M, Chiarion-Sileni, V, Grob, J J, Dummer, R, Wolchok, J D, Schmidt, H, Hamid, O, Robert, C, Ascierto, P A, Richards, J M, Lebbe, C, Ferraresi, V, Smylie, M, Weber, J S, Maio, M, Hosein, F, de Pril, V, Kicinski, M, Suciu, S & Testori, A 2019, ' Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma : long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial ', European Journal of Cancer, vol. 119, pp. 1-10 . https://doi.org/10.1016/j.ejca.2019.07.001Test

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Skin Neoplasms, 610 Medicine & health, Ipilimumab, Kaplan-Meier Estimate, Placebo, Adjuvant therapy, Metastasis, Long-term results, Melanoma, Phase III trial, Stage III, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Humans, 1306 Cancer Research, Aged, Aged, 80 and over, business.industry, Hazard ratio, 10177 Dermatology Clinic, Cancer, Middle Aged, Prognosis, medicine.disease, Discontinuation, 030104 developmental biology, Chemotherapy, Adjuvant, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Female, 2730 Oncology, business, Follow-Up Studies, medicine.drug

الوصف: Background: Since 2015, adjuvant therapy with ipilimumab is an approved treatment for stage III melanoma based on a significantly prolonged recurrence-free survival (RFS). At a median follow-up of 5.3 years, RFS, distant metastasis-free survival (DMFS) and overall survival (OS) were each significantly prolonged in the ipilimumab group compared with the placebo group, despite a 53.3% (ipilimumab) versus 4.6% (placebo) treatment discontinuation rate due to adverse events. We present now long-term follow-up results of this European Organisation for Research and Treatment of Cancer 18071 trial. Patients, methods and results: A total of 99 sites randomised 951 patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) with adequate resection of lymph nodes to receive intravenous infusions of ipilimumab 10 mg/kg or placebo, every 3 weeks for 4 doses, then every 3 months for up to 3 years. The RFS, DMFS and OS, as reported by the local investigators, were assessed by the intention-to-treat analysis. Among 431 patients randomised at 63 sites and who were still alive at the analysis reported in 2016, recent follow-up information could be obtained for 264 patients. The median OS follow-up was 6.9 years. The RFS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.63–0.88; P < 0.001), DMFS (HR: 95% CI: 0.76, 0.64–0.90; P = 0.002) and OS (HR: 0.73, 95% CI: 0.60–0.89; P = 0.002) benefit observed in the ipilimumab group was durable with an 8.7% absolute difference at 7 years for OS. The benefit was consistent across subgroups. Conclusions: Adjuvant therapy with ipilimumab prolongs RFS, DMFS and OS significantly. The benefit is sustained long term and consistent across subgroups.

وصف الملف: 806_Eggermont_A._et_al._Adjuvant_ipilimumab_versus_placebo_after_complete_resection_of_stage_III_melanoma_etc._EJC_2019.pdf - application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::211084f57afa1977a4f55abb0eae48ceTest
https://doi.org/10.1016/j.ejca.2019.07.001Test

المؤلفون: Mario Mandalà, Juliette Murris, Paola Queirolo, Ana Arance, Caroline Dutriaux, Helen Gogas, Gabriella Liszkay, Ralf Gutzmer, Claus Garbe, Keith T. Flaherty, Abir Tadmouri Sellier, Naoya Yamazaki, Jeanne Suissa, Ivana Krajsová, Vanna Chiarion Sileni, Caroline Robert, Reinhard Dummer, Groot Jan de Willem, Paolo A. Ascierto, Ashwin Gollerkeri, Carmen Loquai, Dirk Schadendorf

المساهمون: University of Zurich

مصطلحات موضوعية: Male, 0301 basic medicine, Cancer Research, Skin Neoplasms, Health-related quality of life, Medizin, Hospitalisation rate, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Antineoplastic Combined Chemotherapy Protocols, Vemurafenib, Melanoma, Aged, 80 and over, Sulfonamides, 10177 Dermatology Clinic, Binimetinib, Middle Aged, Progression-Free Survival, humanities, Oncology, Tolerability, 030220 oncology & carcinogenesis, Female, Open label, medicine.drug, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, 610 Medicine & health, BRAF(V600E−K) mutant Melanoma, Young Adult, 03 medical and health sciences, BRAF/MEK inhibitors Combination, Internal medicine, medicine, Humans, In patient, Encorafenib plus binimetinib, Aged, business.industry, Repeated measures design, medicine.disease, 030104 developmental biology, chemistry, Mutation, Quality of Life, Benzimidazoles, Carbamates, business

الوصف: In COLUMBUS, treatment with encorafenib plus binimetinib in patients with advanced BRAF-mutant melanoma showed improved progression-free and overall survival with favourable tolerability compared to vemurafenib treatment. Here, results on health-related quality of life (HRQoL) are presented.COLUMBUS was a two-part, open-label, randomised, phase III study in patients with BRAF-mutant melanoma. In PART-I, 577 patients were randomised (1:1:1) to encorafenib plus binimetinib, encorafenib or vemurafenib. The primary objective was to assess progression-free survival. As a secondary objective, HRQoL was assessed by the EQ-5D, the EORTC QLQ-C30 and the FACT-M questionnaires. Furthermore, time to definitive 10% deterioration was estimated with a Kaplan-Meier analysis and differences in mean scores between groups were calculated with a mixed-effect model for repeated measures. Hospitalisation rate and the impact of hospitalisation on HRQoL were also assessed.Patients receiving the combination treatment showed improvement of their FACT-M and EORTC QLQ-C30 global health status scores, compared to those receiving vemurafenib (post-baseline score differences: 3.03 [p 0.0001] for FACT M and 5.28 [p = 0.0042] for EORTC QLQ-C30), indicative of a meaningful change in patient's status. Furthermore, a delay in the deterioration of QoL was observed in non-hospitalised patients compared to hospitalised patients (hazard ratio [95% CI]: 1.16 [0.80; 1.68] for EORTC QLQ-C30 and 1.27 [0.81; 1.99] for FACT-M) and a risk reduction of 10% deterioration, favoured the combination in both groups.The improved efficacy of encorafenib plus binimetinib compared to vemurafenib, translates into a positive impact on the perceived health status as assessed by the HRQoL questionnaires. The study is registered with ClinicalTrials.gov, number NCT01909453 and EudraCT number 2013-001176-38.

وصف الملف: 898_Gogas_H._et_al._Quality_of_life_in_patients_with_BRAF_mutant_melanoma_receiving_the_combination_encorafenib_plus_binimetinib_EJC_2021.pdf - application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00b598bc6b0d5210f8adf8a69fd7b47bTest
https://www.zora.uzh.ch/id/eprint/203982Test/

المؤلفون: Christoph Hoeller, Marie-Francoise Avril, Pietro Quaglino, François Aubin, Lars Bastholt, Takashi Inozume, Virginia Ferraresi, Michael B. Jameson, Kevin B. Kim, Oliver Bechter, Dirk Schadendorf, Kenji Yokota, Carmen Loquai, Maria-Jose Passos, Inge Marie Svane, Michele Maio, Catherine Barrow, Frank Meiss, Nageatte Ibrahim, Andrzej Mackiewicz, Phillip Parente, Tatsuya Takenouchi, Caroline Dutriaux, Piotr Rutkowski, Alfonsus J M van den Eertwegh, Paola Queirolo, Catriona M. McNeil, Peter Mohr, Felix Kiecker, Susana Puig, Friedegund Meier, Lutz Kretschmer, Alexander C.J. van Akkooi, Alex Menzies, Timothy Crook, Christian U. Blank, Suzana Matkovic, Michael C. Brown, Ragini R. Kudchadkar, Max Levin, Rüdiger Hein, Tanja Skytta, Gerald P. Linette, Clemens Krepler, Adnan Khattak, Ernest Marshall, Joseph Kerger, Oddbjorn Straume, Laurent Mortier, Jochen Utikal, Micaela Hernberg, James Larkin, Yoshio Kiyohara, Mario Mandalà, Henrik Schmidt, Daniil Stroyakovskiy, Pablo Luis Ortiz Romero, Naoya Yamazaki, John Walker, Anna Maria Di Giacomo, Lionel Geoffrois, Jean-Philippe Lacour, Caroline Robert, Vincent Descamps, Shahneen Sandhu, Gil Bar-Sela, Paul C. Nathan, Marcin Dzienis, Ralf Gutzmer, Claus Garbe, Andrey Meshcheryakov, Patrick Combemale, Martin Fehr, Guzel Mukhametshina, Helena Kapiteijn, Geke A. P. Hospers, Jun Aoi, Andrew Haydon, Rutger H. T. Koornstra, Marie-Thérèse Leccia, Sigrun Hallmeyer, Pier Francesco Ferrucci, Jean-Jacques Grob, Leonel Hernandez-Aya, Jan-Christoph Simon, Vanna Chiarion Sileni, Alain Algazi, Lidija Sekulovic, Sandrine Marreaud, Bernard Fitzharris, Jacob Schachter, Xinni Song, Wolf-Henning Boehncke, Rahima Jamal, Paul Lorigan, Maureen J.B. Aarts, Reinhard Dummer, Mike McCrystal, César Martins, Reiner Hofmann-Wellenhof, Alexander M.M. Eggermont, Carola Berking, Elaine Dunwoodie, Bernard Guillot, Michal Kicinski, Philippe Saiag, Céleste Lebbé, Thierry Lesimple, Stefan Suciu, Michal Lotem, Paula Ferreira, Mohammed M. Milhem, Laurent Machet, Patrick Terheyden, Anna Katharina Winge-Main, Peter Hersey, Jean-Francois Baurain, Axel Hauschild, Stéphane Dalle, Jean-Philippe Arnault, Paolo A. Ascierto, Gerard Groenewegen, Florent Grange, Georgina V. Long, Victoria Atkinson, Philippa Corrie, Matteo S. Carlino, Thomas Jouary, Daniel Hendler, Richard Casasola, Ashita Waterston, Jessica C. Hassel

المساهمون: University Medical Center [Utrecht], Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], The University of Sydney, Princess Alexandra Hospital, Brisbane, University of Queensland [Brisbane], Centre Léon Bérard [Lyon], 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), N.N. Blokhin National Medical Research Center of Oncology, Edith Cowan University (ECU), Royal Marsden NHS Foundation Trust, Universitat de Barcelona (UB), Instituto de Salud Carlos III [Madrid] (ISC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Radboud University Medical Center [Nijmegen], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University Hospital of Siena, Amsterdam UMC - Amsterdam University Medical Center, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Merck & Co. Inc, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Internal medicine, CCA - Cancer Treatment and quality of life

المصدر: EORTC Melanoma Group 2021, ' Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial ', The Lancet Oncology, vol. 22, no. 5, pp. 643-654 . https://doi.org/10.1016/S1470-2045Test(21)00065-6
Lancet Oncology, 22, 643-654
Lancet Oncology, 22, 5, pp. 643-654
Lancet Oncology
Lancet Oncology, 2021, 22 (5), pp.643-654. ⟨10.1016/S1470-2045(21)00065-6⟩
The Lancet Oncology, 22(5), 643-654. Lancet Publishing Group

مصطلحات موضوعية: Male, Skin Neoplasms, Medizin, Pembrolizumab, law.invention, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], MESH: Aged, 80 and over, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, 80 and over, MESH: Double-Blind Method, 030212 general & internal medicine, Neoplasm Metastasis, Humanized, Melanoma, MESH: Aged, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Hazard ratio, MESH: Neoplasm Staging, Middle Aged, Oncology, 030220 oncology & carcinogenesis, Female, Adult, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Humans, Neoplasm Staging, medicine.medical_specialty, MESH: Melanoma, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, Antibodies, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Adjuvant therapy, education, Cancer staging, MESH: Humans, business.industry, MESH: Skin Neoplasms, MESH: Adult, MESH: Neoplasm Metastasis, MESH: Male, Clinical trial, MESH: Antibodies, Monoclonal, Humanized, business, MESH: Female

الوصف: Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43–0·74], p1 mm), IIIB, or IIIC (without in-transit metastasis), and with an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) via a central interactive voice response system to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. Randomisation was stratified according to disease stage and region, using a minimisation technique, and clinical investigators, patients, and those collecting or analysing the data were masked to treatment assignment. The two coprimary endpoints were recurrence-free survival in the intention-to-treat (ITT) population and in patients with PD-L1-positive tumours. The secondary endpoint reported here was distant metastasis-free survival in the ITT and PD-L1-positive populations. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37. Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to receive either pembrolizumab (n=514) or placebo (n=505). At an overall median follow-up of 42·3 months (IQR 40·5–45·9), 3·5-year distant metastasis-free survival was higher in the pembrolizumab group than in the placebo group in the ITT population (65·3% [95% CI 60·9–69·5] in the pembrolizumab group vs 49·4% [44·8–53·8] in the placebo group; HR 0·60 [95% CI 0·49–0·73]; p

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca46af8de45fdf5ffd9d70f717e94208Test
https://research.vumc.nl/en/publications/8aae177c-dfa8-4325-b8c2-e7b1d7339027Test