180 results on '"P.A. Ascierto"'
Search Results
52. Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors
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Nicola Mozzillo, Federica Marenco, Paolo Curatolo, A. De Paoli, Luca Giovanni Campana, Lorenzo Borgognoni, P.A. Ascierto, Stefania Bucher, Michele Guida, Alessandro Testori, Simone Mocellin, Carlo Riccardo Rossi, Roberta Rotunno, Antonio Bonadies, Pietro Quaglino, Massimo Framarini, and G.L. De Salvo
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Male ,Oncology ,Electrochemotherapy ,Skin Neoplasms ,Kaplan-Meier Estimate ,Injections, Intralesional ,030207 dermatology & venereal diseases ,Breast cancer ,0302 clinical medicine ,Squamous cell carcinoma ,Medicine ,Prospective Studies ,Prospective cohort study ,Melanoma ,Aged, 80 and over ,Sarcoma ,General Medicine ,Middle Aged ,Cutaneous metastases ,Basal cell carcinoma ,Treatment Outcome ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,Breast carcinoma ,Adult ,medicine.medical_specialty ,Antineoplastic Agents ,Breast Neoplasms ,Bleomycin ,Young Adult ,03 medical and health sciences ,Internal medicine ,Carcinoma ,Humans ,Sarcoma, Kaposi ,Aged ,Proportional Hazards Models ,business.industry ,medicine.disease ,Carcinoma, Basal Cell ,Surgery ,Cisplatin ,business - Abstract
BackgroundCutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened.MethodsThis prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire).ResultsWe enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p
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- 2016
53. Nivolumab (NIVO) versus ipilimumab (IPI) dans le traitement adjuvant du mélanome réséqué de stade III/IV: résultats d’efficacité à 3 ans et analyse de biomarqueurs issus de l’essai de phase 3 CheckMate 238
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Hao Tang, Maurice Lobo, C. Lance Cowey, Michele Maio, Abdel Saci, Mario Mandalà, S. Dalle, Mark R. Middleton, J.M.G. Larkin, Michael Schenker, Ivan Marquez-Rodas, M. Del Vecchio, A. Arance, J.-J. Grob, V. de Pril, J.S. Weber, P.A. Ascierto, V. Chiarion Sileni, Helen Gogas, and Marcus O. Butler
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Dermatology - Abstract
Introduction L’etude de phase 3 CheckMate 238 a demontre une amelioration de la survie sans recidive (SSR) avec NIVO 3 mg/kg vs IPI 10 mg/kg chez les patients (pts) atteints d’un melanome reseque de stade III/IV. Une efficacite maintenue a 24 mois de suivi avec NIVO vs IPI avait ete precedemment rapportee. Nous presentons ici une analyse a 36 mois des donnees d’efficacite et de biomarqueurs (bmq) issus de cette etude. Materiel et methodes Des pts âges de ≥ 15 ans avec un melanome de stade IIIB/C ou IV completement reseque ont ete randomises selon un rapport 1: 1 pour recevoir NIVO (3 mg/kg toutes les 2 semaines (sem); N = 453) ou IPI (10 mg/kg toutes les 3 sem pour 4 doses puis toutes les 12 sem; N = 453) pendant ≤ 1 an ou jusqu’a recidive de la maladie/toxicite inacceptable. La SSR etait le critere d’evaluation principal; les criteres d’evaluation exploratoires comprenaient la survie sans metastases a distance (SSMD) chez les pts atteints d’une maladie de stade III et des bmq d’efficacite potentiels. Resultats A 36 mois de suivi, NIVO continue a demontrer une SSR > vs IPI (HR, 0,68; p Conclusion A 36 mois de suivi, NIVO est toujours associe a une efficacite superieure a celle de l’IPI chez les patients atteints d’un melanome de stade III/IV presentant un risque eleve de recidive dans tous les sous-groupes de pts. Des analyses supplementaires utilisant des scores composites de combinaisons de bmq seront presentees.
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- 2019
54. Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion
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J.-J. Grob, Nicole Basset-Seguin, R. Dummer, John T. Lear, Joseph Malvehy, Dirk Schadendorf, R Krattinger, Axel Hauschild, Brigitte Dréno, P.A. Ascierto, Ralf Gutzmer, Claus Garbe, University hospital of Zurich [Zurich], Istituto Nazionale Tumori IRCCS Fondazione G. Pascale [Naples, Italy] (INT-FGP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), University of Tübingen, Hannover Medical School [Hannover] (MHH), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Salford Royal NHS Foundation Trust [Salford, UK], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Dupuis, Christine, University of Zurich, and Dummer, R
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Oncology ,medicine.medical_specialty ,Skin Neoplasms ,Pyridines ,[SDV]Life Sciences [q-bio] ,Medizin ,Vismodegib ,610 Medicine & health ,Antineoplastic Agents ,Dermatology ,Sonidegib ,law.invention ,2708 Dermatology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Medicine ,Humans ,Basal cell carcinoma ,Anilides ,Hedgehog Proteins ,Adverse effect ,Expert Testimony ,business.industry ,Biphenyl Compounds ,10177 Dermatology Clinic ,2725 Infectious Diseases ,medicine.disease ,[SDV] Life Sciences [q-bio] ,Biphenyl compound ,Infectious Diseases ,chemistry ,Tolerability ,Response Evaluation Criteria in Solid Tumors ,Carcinoma, Basal Cell ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
International audience; Sonidegib and vismodegib are hedgehog pathway inhibitors (HhIs) approved for the treatment of advanced basal cell carcinoma (BCC). Until recently, vismodegib was the only targeted treatment available for patients with locally advanced BCC (laBCC) in cases where surgery and radiotherapy are inappropriate. Sonidegib has recently been approved and now presents an alternative treatment option. The clinical differences between the two HhIs in patients with laBCC are unclear, as no head-to-head randomized controlled trials are or will be initiated. Moreover, there were important differences in the designs of their pivotal studies, BOLT (sonidegib) and ERIVANCE (vismodegib), and these differences complicate evidence-based analysis of their relative efficacy and safety profiles. In this paper, a group of clinical experts in the management of laBCC summarizes the clinical and pharmacological profiles of sonidegib and vismodegib based on published data and their own clinical experience. One key difference between the two pivotal studies was the criteria used to assess BCC severity. ERIVANCE (a single-arm phase II trial) used the conventional Response Evaluation Criteria in Solid Tumors (RECIST), while the more recent double-blind randomized BOLT trial used the stringent modified RECIST (mRECIST). A pre-planned analysis adjusted the outcomes from BOLT with RECIST-like criteria and this enabled the experts to discuss relative efficacy outcomes for the two treatments. Centrally reviewed objective response rate (ORR) for vismodegib was 47.6% (95% CI 35.5-60.6) at 21-month follow-up using RECIST. After adjusting with RECIST-like criteria, the ORR for sonidegib according to central review at 18-month follow-up was 60.6% (95% CI 47.8-72.4). Both treatments were associated with similar patterns of adverse events. Sonidegib and vismodegib share the same efficacy and tolerability profiles, but their pharmacokinetic profiles show several differences, such as volume of distribution and half-life. Further studies are needed to understand how these differences may impact clinical practice.
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- 2019
55. PCN40 Healthcare Resource Utilization in Patients Treated with Encorafenib PLUS Binimetinib for BRAF-Mutant Metastatic Melanoma: DATA from Columbus, a Phase 3 Trial in BRAF-Mutant Melanoma
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A. Tadmouri, P.A. Ascierto, Ashwin Gollerkeri, R. Gutzmer, Keith T. Flaherty, Ivana Krajsová, Dirk Schadendorf, Michael D Pickard, Mario Mandalà, C. Dutriaux, A. Arance, Carmen Loquai, G. Liszkay, Claus Garbe, R. Dummer, V. Chiarion Sileni, Helen Gogas, and C. Robert
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Metastatic melanoma ,business.industry ,Health Policy ,Melanoma ,Mutant ,Public Health, Environmental and Occupational Health ,Binimetinib ,medicine.disease ,chemistry.chemical_compound ,chemistry ,Encorafenib ,Cancer research ,medicine ,In patient ,business ,Resource utilization - Published
- 2020
56. 79O Clinical performance of Immunoscore® in early colon cancer in the Asian population
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Youhan Wang, Jérôme Galon, P.A. Ascierto, Carlo Bifulco, H. Vora, A. Hartmann, Michael H.A. Roehrl, Franck Pagès, Toshihiko Torigoe, Eva Zavadova, Iris D. Nagtegaal, Yutaka Kawakami, Alessandro Lugli, P. Patel, Bernhard Mlecnik, F. Marliot, Pamela S. Ohashi, M. Van den Eynde, Francesco M. Marincola, Bernard A. Fox, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, and UCL - (SLuc) Service d'oncologie médicale
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Oncology ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,Internal medicine ,medicine ,Clinical performance ,Asian population ,Hematology ,business ,medicine.disease - Abstract
Background Immunoscore® is an in vitro diagnostic test predicting the risk of relapse in early-stage Colon Cancer (CC), by measuring the host immune response at the tumor site. This risk-assessment tool provides independent and superior prognostic value than the usual risk parameters and is intended to be used as an adjunct to the TNM classification for clinical decision. In the present study, we investigated Immunoscore® clinical performance in the Asian population from the international SITC-led validation study (Pagès et al. The Lancet 2018). Methods Out of the 2681 eligible stage I-III patients of the international Immunoscore® study, 423 were collected from 4 expert centers in Asia including Japan (n=330), China (n=35), and India (n=58). Patients were classified by Immunoscore® based on pre-defined cutoffs, either in 5 (IS 0-4) or 2 categories: IS Low (IS 0-1) and IS High (IS 2-4). Time to recurrence (TTR) was compared between Immunoscore® categories. Results Immunoscore® Low and High were observed in 37% (n=158) and 63% (n=265) of the Asian cohort, respectively. Immunoscore® was positively and significantly correlated with TTR. After 5 years, 86.9% (95% CI 82.7-91.4), and 77% (95% CI 70,5-84,1) of Immunoscore -High and -Low patients respectively were event free (HR =0.52; 95% CI 0.32-0.86; p=0.0085). When adjusting the model with Immunoscore®, age, gender, T-stage, N-stage, sidedness and MSI, and when stratified by center, Immunoscore® remained a significant parameter (HR=0.45; 95% CI 0.22-0.91; p=0.027). When stratified into 5 Immunoscore® categories, TTR rates at 5 years were 100%, 96%, 84%, 80%, and 73.5% for IS4, IS3, IS2, IS1, IS0, respectively. These results were similar to those found in European and North American patients. Conclusions Immunoscore® is a strong prognostic indicator of the risk of recurrence in stage I-III CC patients who receive standard of care treatment in real-life clinical practice in Asia. This first standardized immune-based assay risk assessment tool can be used reliably to guide clinical decision according to each patient information.
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- 2020
57. 491P Neoadjuvant nivolumab in early stage colorectal cancer
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N. Zanaletti, Carlo Vitagliano, P.A. Ascierto, Jérôme Galon, Paolo Delrio, Alfredo Budillon, E. Di Gennaro, A. Avallone, S. De Franciscis, A. De Stefano, I. Boquet, Secondo Lastoria, Susan Costantini, Fabiana Tatangelo, Diana Giannarelli, A. Cassata, Ugo Pace, Francesca Collina, Vincenza Granata, and Aurelie Catteau
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Oncology ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,Internal medicine ,medicine ,Hematology ,Nivolumab ,Stage (cooking) ,business ,medicine.disease - Published
- 2020
58. 1137P Incidence and time course of adverse events (AEs) with atezolizumab (A) in combination with vemurafenib (V) and cobimetinib (C) in the phase III IMspire150 study
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L. de la Cruz Merino, Judit Oláh, V. McNally, P.A. Ascierto, Haocheng Li, C. Robert, Karl D. Lewis, Q. Zhu, Jacek Mackiewicz, Grant A. McArthur, Rodrigo Ramella Munhoz, Edward McKenna, R. Gutzmer, Paola Queirolo, and G. Liszkay
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Oncology ,Cobimetinib ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Hematology ,chemistry.chemical_compound ,chemistry ,Atezolizumab ,Internal medicine ,Time course ,medicine ,Vemurafenib ,Adverse effect ,business ,medicine.drug - Published
- 2020
59. LBA43 Spartalizumab plus dabrafenib and trametinib (Sparta-DabTram) in patients (pts) with previously untreated BRAF V600–mutant unresectable or metastatic melanoma: Results from the randomized part 3 of the phase III COMBI-i trial
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C. Dutriaux, Aisha Masood, P.A. Ascierto, Antoni Ribas, Keith T. Flaherty, Eduard Gasal, Jan C. Brase, Paul Lorigan, H.A. Tawbi, Steven H. Green, Pier Francesco Ferrucci, Mario Mandalà, C. Robert, Piotr Rutkowski, O. Leonov, Georgina V. Long, Paul Nathan, Dirk Schadendorf, Tomas Haas, and Reinhard Dummer
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Trametinib ,Oncology ,medicine.medical_specialty ,Metastatic melanoma ,business.industry ,Mutant ,Dabrafenib ,Hematology ,Internal medicine ,Medicine ,In patient ,business ,medicine.drug - Published
- 2020
60. 1102P Clinical benefit in BRAFV600 mutation-positive melanoma defined by programmed death ligand 1 (PD-L1) and/or lactate dehydrogenase (LDH) status: Exploratory analyses from the IMspire150 study
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P.A. Ascierto, Harper Forbes, Lev V. Demidov, Rodrigo Perez Pereira, Kalpit Shah, Yibing Yan, Svetlana Protsenko, Thomas Eigentler, Piotr Rutkowski, Helen Gogas, G. Moiseevich Manikhas, Caroline Robert, Daniil Stroyakovskiy, V. McNally, Karl D. Lewis, Ralf Gutzmer, and Grant A. McArthur
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biology ,business.industry ,Melanoma ,Hematology ,Ligand (biochemistry) ,medicine.disease ,chemistry.chemical_compound ,Oncology ,chemistry ,PD-L1 ,Lactate dehydrogenase ,Mutation (genetic algorithm) ,biology.protein ,Cancer research ,Medicine ,business ,Programmed death - Published
- 2020
61. LBA46 Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: Final results regarding distant metastasis-free survival from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial
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V. Atkinson, Andrew Haydon, P.A. Ascierto, C. Robert, Christian U. Blank, A.C.J. van Akkooi, Matteo S. Carlino, A. M. M. Eggermont, Clemens Krepler, Stefan Suciu, Adnan Khattak, Andrey Meshcheryakov, Mario Mandalà, Michal Kicinski, Georgina V. Long, Sandrine Marreaud, Nageatte Ibrahim, S. Dalle, S. Puig Sarda, and Shahneen Sandhu
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Oncology ,medicine.medical_specialty ,business.industry ,Double blinded ,Distant metastasis ,Hematology ,Pembrolizumab ,Placebo ,Complete resection ,Internal medicine ,medicine ,Stage III melanoma ,business - Published
- 2020
62. How do immune checkpoint-targeted antibodies work? The need for improved pharmacokinetic evaluation in early phase studies
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Aurélien Marabelle and P.A. Ascierto
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safety ,MEDLINE ,Bioinformatics ,Antibodies ,Miscellaneous Tumors ,PK exposure ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Neoplasms ,Medicine ,Humans ,030212 general & internal medicine ,immuno-oncology ,nivolumab ,biology ,business.industry ,Hematology ,Original Articles ,solid tumors ,Immune checkpoint ,Q4W ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Antibody ,Nivolumab ,Early phase ,business - Abstract
Background A nivolumab monotherapy flat-dosing regimen of 480 mg every 4 weeks (Q4W) has been approved in several markets, including the United States, Canada, and European Union, as an alternative dosing regimen for several indications. Approvals of this Q4W regimen were based on population pharmacokinetic (PK) analyses, established flat exposure–response relationships, and clinical safety. The objective of this study was to compare the PK exposure of 480 mg Q4W with 3 mg/kg every 2 weeks (Q2W) and 240 mg Q2W using modeling and simulation, and to evaluate clinical safety of the Q4W regimen. Patients and methods Nivolumab PK exposure for the 480 mg Q4W schedule was simulated for 3817 patients across multiple tumor types and compared with those for the 3 mg/kg Q2W and 240 mg Q2W schedules. The safety profile of the Q4W schedule was assessed by analysis of clinical data from 61 patients who transitioned to nivolumab 480 mg Q4W from 3 mg/kg Q2W during four phase III clinical trials. Results Compared with 3 mg/kg Q2W, nivolumab 480 mg Q4W produced similar time-averaged concentration, approximately 16% lower trough concentration, and 45% higher peak concentration at steady state. The peak concentration for 480 mg Q4W was significantly lower than that of 10 mg/kg Q2W, a dose previously shown to have an acceptable tolerability and safety profile. Treatment-related adverse events (TRAEs) that started after transitioning from 3 mg/kg Q2W to 480 mg Q4W were reported in 14.8% of patients, with 1.6% of patients reporting grades 3–4 TRAEs. Pooled safety data for these patients are consistent with those for the 3 mg/kg Q2W schedules, and no new safety signals were identified. Conclusions The time-averaged steady-state exposure and safety profile of nivolumab 480 mg Q4W are consistent with that of 3 mg/kg Q2W across multiple tumor types. Nivolumab 480 mg Q4W represents a new dosing schedule option, and in addition to 240 mg Q2W, provides convenience and flexibility for patient care. Clinical trial numbers NCT01721772, NCT01668784, NCT01673867, NCT01642004
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- 2018
63. ILLUMINATE 301: A randomized phase III comparison of IMO-2125 with ipilimumab (ipi) versus ipi alone in subjects with anti PD 1 refractory melanoma
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Carmen Loquai, S. Rahimian, Suzanne Swann, Petr Arenberger, Ahmad A. Tarhini, John Walker, Heather Shaw, Johan Hansson, Victoria Atkinson, Sylvie Negrier, J. Geib, Adi Diab, P.A. Ascierto, and Ellen Kapiteijn
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Oncology ,medicine.medical_specialty ,business.industry ,Melanoma ,Anti pd 1 ,Ipilimumab ,Hematology ,medicine.disease ,Refractory ,Internal medicine ,medicine ,business ,medicine.drug - Published
- 2018
64. Immunoscore predicts significant differences in time to recurrence in stage I colon cancer patients
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A. Hartmann, Iris D. Nagtegaal, Yutaka Kawakami, Carlo Bifulco, Alessandro Lugli, Fabienne Hermitte, P.A. Ascierto, Franck Pages, M. Van den Eynde, Toshihiko Torigoe, Pamela S. Ohashi, Yi Wang, Michael H.A. Roehrl, F. Marliot, P. Patel, Bernhard Mlecnik, Eva Zavadova, Jérôme Galon, Francesco M. Marincola, and Bernard A. Fox
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medicine.medical_specialty ,Multivariate analysis ,business.industry ,Colorectal cancer ,Stock options ,Subgroup analysis ,Risk management tools ,Hematology ,Stage ii ,medicine.disease ,Oncology ,Time to recurrence ,Internal medicine ,Cohort ,medicine ,business - Abstract
Background Immunoscore® is an in vitro diagnostic test that predicts the risk of relapse in patients with Colon Cancer (CC) by measuring the host immune response at the tumor site. It is an immune risk-assessment tool providing independent and superior prognostic value than traditional histopathological risk parameters, and is intended to be used as an adjunct to the TNM classification. Currently, Immunoscore plays a critical role to guide post-surgery decisions in stage II & III CC patients. In stage I, survival rates are high and adjuvant chemotherapy is not typically recommended. However, approximately 10% of stage I CC tumors will recur even after surgical resection. Methods A subgroup analysis was performed on the stage I patients (n = 451) from the Immunoscore international validation study (Pages et al. The Lancet 2018). Patients were classified by Immunoscore based on pre-defined cutoffs, either in 5 (IS 0-4) or in 3 categories: IS Low (IS0-1), Intermediate (IS 2), High (IS 3-4). Time to recurrence (TTR) was compared between Immunoscore categories. Results Immunoscore Low, Intermediate and High were observed in 14%, 47% and 39% of the cohort, respectively. Immunoscore was positively and significantly correlated with TTR. When adjusting the model with Immunoscore, age, gender, T-stage sidedness and MSI, Immunoscore remained the sole significant parameter (stratified by participating center HRlow vs high=7.82; 95% CI 1.49 − 41.01; p = 0.015). In multivariate analysis, the variable with the most important relative contribution to the risk (Chi2) was Immunoscore. The robust correlation between Immunoscore classification and TTR was further corroborated by a separate analysis of the same cohort distributed into five IS categories. In MSS stage I patients, TTR rates at 5 years were 100%, 98.1%, 93.5%, 85.4%, 87.5% for IS4, IS3, IS2, IS1, IS0, respectively. Conclusions Immunoscore® is a robust prognostic indicator of the risk of recurrence in stage I CC. This risk assessment tool reliably identifies a sub-group of patients with an increased risk of relapse for whom a more intensive surveillance program after curative resection may be recommended. Legal entity responsible for the study SITC (Society for ImmunoTherapy of Cancer) / INSERM. Funding Grants from National Institute of Health and Medical Research (INSERM), the LabEx Immuno-oncology, the Transcan ERAnet European project, Association pour la Recherche contre le Cancer, CARPEM, AP-HP, INCA translationnel, Japan-AMED (P-DIRECT) and MEXT (Grants-in-aid for Scientific Research-S), and Ministry of Health of the Czech Republic (AZV CR 15-28188A) Progres Q25-LF1. Disclosure J. Galon: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Co-founder : HalioDx; Research grant / Funding (institution): Perkin-Elmer; Advisory / Consultancy, Research grant / Funding (institution): IObiotech; Advisory / Consultancy, Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Imcheck Therapeutics; Advisory / Consultancy: BMS; Advisory / Consultancy: Northwest Biotherapeutics; Advisory / Consultancy: Amgen; Advisory / Consultancy: Gilead; Advisory / Consultancy: CatalYm GmbH; Advisory / Consultancy: Sanofi; Licensing / Royalties, Patent holder: INSERM. F. Hermitte: Shareholder / Stockholder / Stock options, Full / Part-time employment, Co-founder : HalioDx. B. Mlecnik: Licensing / Royalties, Patent holder: INSERM. F. Pages: Licensing / Royalties, Patent holder: INSERM. All other authors have declared no conflicts of interest.
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- 2019
65. PCN84 COST OF ILLNESS OF CUTANEOUS SQUAMOUS CELL CARCINOMA IN ITALY
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Andrea Marcellusi, P.A. Ascierto, C. Bini, F.S. Mennini, and K. Peris
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medicine.medical_specialty ,Cutaneous squamous cell carcinoma ,business.industry ,Health Policy ,Public Health, Environmental and Occupational Health ,Cost of illness ,Medicine ,business ,Dermatology - Published
- 2019
66. Adjuvant nivolumab (NIVO) versus ipilimumab (IPI) in resected stage III/IV melanoma: 3-year efficacy and biomarker results from the phase III CheckMate 238 trial
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J.-J. Grob, V. Chiarion-Sileni, Mario Mandalà, Jeffrey S. Weber, Maurice Lobo, J.M.G. Larkin, Abdel Saci, Ana Arance, M. Del Vecchio, V. de Pril, Ivan Marquez-Rodas, P.A. Ascierto, Stéphane Dalle, Marcus O. Butler, Michele Maio, Michael Schenker, Charles Lance Cowey, Helen Gogas, T. Tang, and Mark R. Middleton
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Oncology ,medicine.medical_specialty ,Surrogate endpoint ,business.industry ,medicine.medical_treatment ,Melanoma ,Cancer ,Ipilimumab ,Hematology ,medicine.disease ,Internal medicine ,medicine ,Biomarker (medicine) ,Nivolumab ,Stage (cooking) ,business ,Adjuvant ,medicine.drug - Published
- 2019
67. ILLUMINATE 301: A randomized phase III study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
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G.K. In, Adi Diab, Sandrine Mansard, John Walker, Johan Hansson, P.A. Ascierto, Tina Cheng, Marcus O. Butler, Sylvie Negrier, J.-J. Grob, Carmen Loquai, Ivana Krajsová, Victoria Atkinson, Ellen Kapiteijn, Massimo Guidoboni, C. Robert, Heather Shaw, and M. Mehta
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business.industry ,Anti pd 1 ,Stock options ,Hematology ,Tlr agonists ,Management ,Oncology ,Honorarium ,Medicine ,media_common.cataloged_instance ,In patient ,Cns disease ,European union ,business ,Advanced melanoma ,media_common - Abstract
Background Tilsotolimod (IMO-2125) is a Toll-like receptor (TLR) 9 agonist with potent immunostimulating activity. In an ongoing phase I/II clinical study in patients with advanced melanoma who progressed on or after anti-PD-1 therapy (NCT02644967), intratumoral (IT) tilsotolimod with ipilimumab was well-tolerated, demonstrating durable responses (including complete response >21 months), dendritic cell activation, type I interferon response, CD8+ T-cell proliferation in responders, and an abscopal effect.1-2 Trial design ILLUMINATE 301 (NCT03445533) is a randomized phase III global, multi-center, open-label study of IT tilsotolimod (8 mg) in combination with ipilimumab (3 mg/kg) versus ipilimumab monotherapy in patients with advanced melanoma and progression on or after anti-PD-1 therapy. Eligible patients are ≥18 years with histologically confirmed unresectable Stage III or Stage IV melanoma, ≥1 measurable lesion accessible for injection (superficial or visceral, the latter with image guidance), ECOG PS ≤ 1, and adequate organ function. Exclusion criteria include prior TLR agonists, prior ipilimumab (except adjuvant ≥12 weeks before progression), and CNS disease other than stable brain metastases. Patients are randomized 1:1 and stratified by duration of prior antiPD-1 (≥12 weeks vs Clinical trial identification NCT03445533. Editorial acknowledgement Ted Everson, Idera Pharmaceuticals, Inc. Legal entity responsible for the study Idera Pharmaceuticals, Inc. Funding Idera Pharmaceuticals, Inc. Disclosure M.O. Butler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Merck; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Immunovaccine; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: GSK; Advisory / Consultancy: Genzyme; Honoraria (self): Roche; Research grant / Funding (self): Takara Bio. C. Robert: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Merck Serono. S. Negrier: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EUSA Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis. G.K. In: Advisory / Consultancy: Bristol-Myers Squibb. J. Walker: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck Serono; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self): Merck/MSD. V.G. Atkinson: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck/MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Travel / Accommodation / Expenses: OncoSec. J. Hansson: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Bristol-Myers Squibb. E. Kapiteijn: Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Roche. C. Loquai: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: Idera. H.M. Shaw: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses: Genmab; Research grant / Funding (institution), Travel / Accommodation / Expenses: Idera; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: Iovance Biotherapeutics. T. Cheng: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD. S. Mansard: Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Pierre Fabre. J.J. Grob: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Merck Serono. M. Mehta: Shareholder / Stockholder / Stock options, Full / Part-time employment: Idera Pharmaceuticals. P.A. Ascierto: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Array BioPharma; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Newlink Genetics; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MedImmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Syndax; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Idera; Advisory / Consultancy: Ultimovacs; Advisory / Consultancy: Sandoz; Advisory / Consultancy: Immunocore.A. Diab: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Nektar; Advisory / Consultancy: CureVac; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Idera; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.
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- 2019
68. Systemic gut microbial metabolites limit the anti-tumour effect of CTLA-4 blockade in hosts with cancer
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C. Robert, Jean Mehdi Jouniaux, Patrick Saulnier, Nathalie Chaput, Franck Carbonnel, Ludovic Lacroix, Clélia Coutzac, Angelo Paci, V. Asvatourian, and P.A. Ascierto
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medicine.medical_specialty ,Metastatic melanoma ,business.industry ,Hematology ,Advanced cancer ,Peripheral blood ,Anti tumour ,Oncology ,Aldesleukin ,Family medicine ,Molecular mechanism ,Medicine ,In patient ,Dietary fiber ,business - Abstract
Background Gut microbiota composition might influence the clinical benefit of immune checkpoints in patients with advanced cancer but mechanisms underlying this relationship remained unclear. Molecular mechanism whereby the gut microbiota influences immune responses is mainly assigned to gut microbial metabolites. The main metabolites of the gut microbiota are short-chain fatty acids (SCFAs), which are produced in large amounts in the colon through bacterial fermentation of dietary fiber. We evaluated in mice and in patients treated with anti-CTLA-4 if SCFAs levels could be related to the clinical outcome. Methods Thirty-nine patients with metastatic melanoma were treated with ipilimumab were prospectively enrolled. Fecal microbiota composition was assessed using 16S metagenomic analysis and quantitative PCR (Q-PCR) analyses for Faecalibacterium prausnitzii (F. prausnitzii) at baseline. Stool and serum concentrations of acetate, propionate and butyrate were also evaluated in two independent cohorts in accordance with clinical outcomes. Peripheral blood lymphocytes immunophenotypes were studied in parallel. The anti-CTLA-4 anti-tumor effect was also evaluated in mice models in with or without butyrate supplementation. Results Systemic butyrate was linked to Faecalibacterium prausnitzii enrichment in the stool of patients. High blood SCFAs levels (mainly propionate or butyrate) were associated with resistance to CTLA-4 blockade and were associated with a rise of Treg cells. During the course of anti-CTLA-4 treatment, butyrate limited the up-regulation of CD80/CD86 expression on dendritic cells, the induction of tumor-specific T cells and the accumulation of memory T cells in mice with cancer. In patients, restricted accumulation of memory T cells and IL-2 impregnation after ipilimumab treatment was observed. Conclusions Altogether, these results suggested that gut microbial metabolites might favor an immune tolerance profile that limits anti-CTLA-4 activity. Legal entity responsible for the study Institut Gustave Roussy. Funding This study was funded by Gustave Roussy Cancer Campus, Fondation Gustave Roussy, the Institut national de la sante et de la recherche medicale (INSERM), the Centre national de la recherche scientifique (CNRS), SIRIC SOCRATE (INCa DGOS INSERM 6043), SIRIC SOCRATE 2.0 (INCa-DGOS-INSERM_12551), MMO program: ANR-10IBHU-0001); Direction General de l'Offre de Soins (DGOS; TRANSLA 12-174); Institut National du Cancer (INCa; 2012-062 N_ Canceropole: 2012-1-RT-14-IGR-01). Dr. Clelia Coutzac was supported by fellowships from Fondation pour la Recherche Medicale (FRM) from 2015 to 2016. Disclosure C. Coutzac: Honoraria (self): AMGEN; Honoraria (self): Servier. L. Lacroix: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Illumina; Advisory/Consultancy: Qiagen; Advisory/Consultancy: Novartis Thermofisher; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Dyn; Speaker Bureau/Expert testimony: Vela diagnostics; Speaker Bureau/Expert testimony: Luye Pharma. F. Carbonnel: Advisory/Consultancy: enterome; Advisory/Consultancy: Amgen; Advisory/Consultancy: Astra; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Janssen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Abbvie; Advisory/Consultancy: Mayoly Spindler; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pileje; Advisory/Consultancy: Roche. P.A. Ascierto: Advisory/Consultancy: Bristol Myers-Squibb; Advisory/Consultancy, Research grant/Funding (self): Roche-Genentech; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (self): Array; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Incyte; Advisory/Consultancy: NewLink Genetics; Advisory/Consultancy: Genmab; Advisory/Consultancy: Medimmune; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Syndax; Advisory/Consultancy: SunPharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Idera. C. Robert: Advisory/Consultancy: Roche; Advisory/Consultancy: GSK; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: BMS. N. Chaput: Research grant/Funding (self): Cytune Pharma; Research grant/Funding (self): GSK; Speaker Bureau/Expert testimony, Research grant/Funding (self): Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca. All other authors have declared no conflicts of interest.
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- 2019
69. Données de survie globale de l’étude COLUMBUS, étude de phase III avec encorafénib (ENCO) plus binimétinib (BINI) versus vémurafénib (VEM) ou encorafénib (ENCO) dans le mélanome métastatique BRAF muté
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J.W.B. de Groot, Naoya Yamazaki, Keith T. Flaherty, G. Liszkay, Carmen Loquai, P.A. Ascierto, Michael D Pickard, L. Moutouh-de Parseval, Ivana Krajsová, Mario Mandalà, Reinhard Dummer, Helen Gogas, Dirk Schadendorf, A. Arance, Ralf Gutzmer, Claus Garbe, Caroline Robert, C. Dutriaux, V. Chiarion Sileni, and V. Sandor
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Dermatology - Abstract
Introduction Un traitement associant des inhibiteurs de BRAF et de MEK est le traitement de reference des melanomes avances porteur d’une mutation BRAFV600. La partie 1 de COLUMBUS evaluait l’inhibiteur de BRAF, encorafenib (ENCO) 450 mg, une fois par jour (QD) + l’inhibiteur de MEK, binimetinib (BINI) 45 mg, 2 fois par jour (BID)–(COMBO450) vs le vemurafenib (VEM) 960 mg BID ou ENCO 300 mg QD (ENCO300) chez des patients (pts) atteints d’un melanome avance porteur d’une mutation BRAFV600. L’objectif principal de l’etude etait la survie sans progression (SSP) ; la SSP mediane etait de 14,9 mois pour COMBO450 vs 7,3 mois pour VEM ; HR : 0,54 (p bilateral Patients et methodes Les pts atteints d’un melanome metastatique porteur d’une mutation BRAFV600, naifs de traitement ou progressant pendant/apres une premiere ligne par immunotherapie etaient stratifies en fonction du stade de la maladie, de l’indice de performance (Eastern Cooperative Oncology Group), et de l’administration d’une premiere ligne d’immunotherapie. Les pts de la partie 1 de COLUMBUS etaient randomises selon un ratio 1 :1 :1 dans le bras COMBO450 (n = 192), ENCO300 (n = 194) ou VEM (n = 191). Les reponses ou progressions tumorales ont ete evaluees en aveugle par un comite central independant. L’analyse de la SG etait planifiee apres 232 evenements dans les bras COMBO450 et VEM combines. Resultats Au total, 105, 106 et 127 evenements ont contribue a l’analyse de la SG dans les bras COMBO450, ENCO300 et VEM, respectivement, avec un suivi median de 21,5 mois. La SG mediane etait de 33,6 mois (IC95 % : 24,4–39,2) avec COMBO450, 23,5 mois (IC95 % : 19,6–33,6) avec ENCO300 et 16,9 mois (IC95 % : 14,0–24,5) avec VEM. Le risque de deces etait reduit avec COMBO450 vs VEM (HR : 0,61 [IC95 % : 0,47–0,79], p nominal bilateral Conclusion La SSP mediane de 14,9 mois et la SG mediane de 33,6 mois, les meilleurs resultats rapportes pour cette classe de traitement, suggerent que la COMBO450 est une nouvelle association prometteuse pour le traitement du melanome BRAF mute.
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- 2018
70. Efficacy and safety of single-agent pan-human epidermal growth factor receptor (HER) inhibitor dacomitinib in locally advanced unresectable or metastatic skin squamous cell cancer
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Roberta Granata, Laura D. Locati, G. Gallino, F. Perrone, Adele Busico, P.A. Ascierto, Rosalba Miceli, Stefano Cavalieri, Marco Palla, Lisa Licitra, Carlo Resteghini, Donata Galbiati, Roberto Patuzzo, Andrea Maurichi, Nicholas Paielli, Salvatore Alfieri, Luigi Mariani, Cristiana Bergamini, Paolo Bossi, and Roberta Ruggeri
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0301 basic medicine ,Oncology ,Neuroblastoma RAS viral oncogene homolog ,Male ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,medicine.medical_treatment ,Dacomitinib ,Skin cancer ,Skin squamous cell carcinoma ,Aged ,Aged, 80 and over ,Biomarkers, Tumor ,Carcinoma, Squamous Cell ,Female ,Follow-Up Studies ,Humans ,Lymphatic Metastasis ,Middle Aged ,Prognosis ,Quinazolinones ,Survival Rate ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Mucositis ,80 and over ,Adverse effect ,Chemotherapy ,Tumor ,business.industry ,Carcinoma ,medicine.disease ,Rash ,Clinical trial ,Radiation therapy ,030104 developmental biology ,chemistry ,Squamous Cell ,030220 oncology & carcinogenesis ,medicine.symptom ,business ,Biomarkers - Abstract
Background In recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial. Methods Patients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR). Tumour samples were analysed through next-generation sequencing using a custom panel targeting 36 genes associated with sSCC. Results Forty-two patients (33 men; median age 77 years) were treated. Most (86%) received previous treatments consisting in surgery (86%), RT (50%) and CT (14%). RR was 28% (2% complete response; 26% partial response), disease control rate was 86%. Median progression-free survival and overall survival were 6 and 11 months, respectively. Most patients (93%) experienced at least one adverse event (AE): diarrhoea, skin rash (71% each), fatigue (36%) and mucositis (31%); AEs grade 3–4 occurred in 36% of pts. In 16% of cases, treatment was discontinued because of drug-related toxicity. TP53, NOTCH1/2, KMT2C/D, FAT1 and HER4 were the most frequently mutated genes. BRAF, NRAS and HRAS mutations were more frequent in non-responders, and KMT2C and CASP8 mutations were restricted to this subgroup. Conclusions In sSCC, dacomitinib showed activity similar to what was observed with anti–epidermal growth factor receptor agents, and durable clinical benefit was observed. Safety profile was comparable to previous experiences in other cancers. Molecular pt selection could improve therapeutic ratio.
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- 2017
71. Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study
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James Larkin, Grant A. McArthur, Jeffrey A. Sosman, C. Robert, Paul B. Chapman, A. Testori, Ivor Caro, Reinhard Dummer, Ilsung Chang, J.B.A.G. Haanen, Paul Lorigan, P.A. Ascierto, Omid Hamid, Antoni Ribas, Shelley Coleman, Keith T. Flaherty, David Hogg, Axel Hauschild, University of Zurich, and Chapman, P B
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0301 basic medicine ,Oncology ,Male ,Indoles ,Skin Neoplasms ,2720 Hematology ,Kaplan-Meier Estimate ,0302 clinical medicine ,80 and over ,Enzyme Inhibitors ,Vemurafenib ,Melanoma ,Cancer ,Aged, 80 and over ,education.field_of_study ,Sulfonamides ,Manchester Cancer Research Centre ,Hazard ratio ,10177 Dermatology Clinic ,Hematology ,Middle Aged ,Alkylating ,3. Good health ,Dacarbazine ,Treatment Outcome ,030220 oncology & carcinogenesis ,Censoring (clinical trials) ,6.1 Pharmaceuticals ,2730 Oncology ,Female ,medicine.drug ,Adult ,Proto-Oncogene Proteins B-raf ,medicine.medical_specialty ,Adolescent ,Population ,Clinical Trials and Supportive Activities ,Oncology and Carcinogenesis ,610 Medicine & health ,Ipilimumab ,dacarbazine ,Antineoplastic Agents ,03 medical and health sciences ,Young Adult ,Clinical Research ,Internal medicine ,medicine ,Humans ,Oncology & Carcinogenesis ,education ,Antineoplastic Agents, Alkylating ,Aged ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Evaluation of treatments and therapeutic interventions ,Original Articles ,medicine.disease ,Confidence interval ,Editor's Choice ,030104 developmental biology ,BRAF mutation ,Mutation ,business - Abstract
Background The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with dacarbazine in treatment-naive patients with BRAFV600 mutation–positive metastatic melanoma. We present final OS data from BRIM-3. Patients and methods Patients were randomly assigned in a 1 : 1 ratio to receive vemurafenib (960 mg twice daily) or dacarbazine (1000 mg/m2 every 3 weeks). OS and PFS were co-primary end points. OS was assessed in the intention-to-treat population, with and without censoring of data for dacarbazine patients who crossed over to vemurafenib. Results Between 4 January 2010 and 16 December 2010, a total of 675 patients were randomized to vemurafenib (n = 337) or dacarbazine (n = 338, of whom 84 crossed over to vemurafenib). At the time of database lock (14 August 2015), median OS, censored at crossover, was significantly longer for vemurafenib than for dacarbazine {13.6 months [95% confidence interval (CI) 12.0–15.4] versus 9.7 months [95% CI 7.9–12.8; hazard ratio (HR) 0.81 [95% CI 0.67–0.98]; P = 0.03}, as was median OS without censoring at crossover [13.6 months (95% CI 12.0–15.4) versus 10.3 months (95% CI 9.1–12.8); HR 0.81 (95% CI 0.68–0.96); P = 0.01]. Kaplan–Meier estimates of OS rates for vemurafenib versus dacarbazine were 56% versus 46%, 30% versus 24%, 21% versus 19% and 17% versus 16% at 1, 2, 3 and 4 years, respectively. Overall, 173 of the 338 patients (51%) in the dacarbazine arm and 175 of the 337 (52%) of those in the vemurafenib arm received subsequent anticancer therapies, most commonly ipilimumab. Safety data were consistent with the primary analysis. Conclusions Vemurafenib continues to be associated with improved median OS in the BRIM-3 trial after extended follow-up. OS curves converged after ≈3 years, likely as a result of crossover from dacarbazine to vemurafenib and receipt of subsequent anticancer therapies. ClinicalTrials.gov NCT01006980.
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- 2017
72. Real-world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab
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A H Hernaez, K S Stevinson, P.A. Ascierto, A A Arance, Reshma Shinde, P K Kaskel, P M Mohr, and G M McArthur
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Male ,medicine.medical_specialty ,Metastatic Cutaneous Melanoma ,Skin Neoplasms ,medicine.medical_treatment ,Ipilimumab ,Dermatology ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Chart review ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Neoplasm Metastasis ,Melanoma ,Aged ,Retrospective Studies ,Chemotherapy ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Europe ,Infectious Diseases ,Treatment Outcome ,030220 oncology & carcinogenesis ,Cohort ,Observational study ,Female ,business ,medicine.drug - Abstract
BACKGROUND There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011. OBJECTIVE To evaluate ipilimumab and postipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain, following regulatory approval. METHODS Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death. RESULTS Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another antimelanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received postipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders. CONCLUSION During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received postipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options.
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- 2017
73. Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial
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N. Dimier, Reinhard Dummer, C. Dutriaux, Lisa Licitra, B. Dréno, Nicole Basset-Seguin, Axel Hauschild, A. Fittipaldo, J.-J. Grob, Rainer Kunstfeld, Luc Thomas, Laurent Mortier, Bernard Guillot, I. Xynos, Johan Hansson, Nicolas Meyer, Kate Fife, A. Raimundo, Emi Dika, Petr Arenberger, P.A. Ascierto, Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Kiel University, Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Unité de Thérapie Cellulaire et Génétique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Unité du cancer de la peau [CHU Nantes], Hôpital Claude Huriez [Lille], CHU Lille, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Basset-Séguin, N., Hauschild, A., Kunstfeld, R., Grob, J., Dréno, B., Mortier, L., Ascierto, P.A., Licitra, L., Dutriaux, C., Thomas, L., Meyer, N., Guillot, B., Dummer, R., Arenberger, P., Fife, K., Raimundo, A., Dika, E., Dimier, N., Fittipaldo, A., Xynos, I., Hansson, J., University of Zurich, Basset-Séguin, N, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Hôpital Claude Huriez, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,Cancer Research ,Spasm ,Time Factors ,Pyridines ,Pyridine ,Basal Cell ,Administration, Oral ,Kaplan-Meier Estimate ,Sonidegib ,Antineoplastic Agent ,030207 dermatology & venereal diseases ,chemistry.chemical_compound ,0302 clinical medicine ,80 and over ,1306 Cancer Research ,Anilides ,Creatine Kinase ,Aged, 80 and over ,Incidence (epidemiology) ,10177 Dermatology Clinic ,Basal Cell Nevus Syndrome ,Middle Aged ,3. Good health ,Gorlin syndrome ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Administration ,Disease Progression ,2730 Oncology ,Female ,Human ,medicine.drug ,Oral ,Adult ,medicine.medical_specialty ,Time Factor ,Adolescent ,Vismodegib ,610 Medicine & health ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Disease-Free Survival ,Drug Administration Schedule ,Hedgehog pathway inhibitor ,STEVIE ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Humans ,Basal cell carcinoma ,Adverse effect ,Aged ,business.industry ,Carcinoma ,Anilide ,medicine.disease ,Discontinuation ,Surgery ,Clinical trial ,chemistry ,Carcinoma, Basal Cell ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,business ,Progressive disease ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology - Abstract
Background The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665 ), assessed safety and efficacy of vismodegib—a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)—in a patient population representative of clinical practice. Primary analysis data are presented. Patients and methods Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points. Results Evaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0–44) months. Most patients (98%) had ≥1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure ≥12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7–71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6–48.1) in patients with metastatic BCC. Conclusions The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. ClinicalTrials.gov NCT01367665 .
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- 2017
74. Electrochemotherapy as 'new standard of care' treatment for cutaneous Kaposi's sarcoma
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P.A. Ascierto, Marialina Tornesello, G. Di Monta, Nicola Mozzillo, Ugo Marone, Corrado Caracò, Ester Simeone, Lucia Benedetto, Franco M. Buonaguro, S. La Padula, Di Monta, G., Caraco, C., Benedetto, L., La Padula, S., Marone, U., Tornesello, M. L., Buonaguro, F. M., Simeone, E., Ascierto, P. A., and Mozzillo, N.
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Adult ,Male ,medicine.medical_specialty ,Electrochemotherapy ,Skin Neoplasms ,Standard of care ,Real-Time Polymerase Chain Reaction ,behavioral disciplines and activities ,Viral Proteins ,medicine ,Humans ,Prospective Studies ,Stage (cooking) ,Sarcoma, Kaposi ,Kaposi's sarcoma ,HHV-8 ,Aged ,Neoplasm Staging ,Aged, 80 and over ,business.industry ,Standard of Care ,General Medicine ,Middle Aged ,medicine.disease ,Dermatology ,Molecular analysis ,Treatment Outcome ,Oncology ,DNA, Viral ,Quality of Life ,Female ,Surgery ,Sarcoma ,business ,Viral load ,Follow-Up Studies ,Blood sampling - Abstract
Background Electrochemotherapy (ECT) is a novel modality for the treatment of skin nodules and cutaneous or subcutaneous tumors that allows delivery of low and non-permeant drug into cells. The aim of this prospective single-center study was to evaluate ECT efficacy in the local treatment of Classic Kaposi's sarcoma (CKS) skin localization stage I-II sec. Brambilla et al. Methods Nineteen consecutive patients affected by classic KS were included in this study. All patients underwent blood sampling and concurrent incisional biopsy for histological diagnosis and Kaposi's sarcoma related herpes virus 8 (HHV-8) molecular analysis. ECT treatment of KS cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE). The primary endpoint of the study was the evaluation of ECT efficacy in the treatment of KS skin nodules and the assessment of HHV-8 viral load in the peripheral blood following the ECT therapy. Results Complete response (CR) was observed in 14 (73.6%) patients after first ECT session, while 3 (15.7%) and 2 (10.5%) out of 19 patients received a second and a third ECT treatment, respectively. Clinical response dragged out the whole follow-up period that ranged between 6 and 31 months with a median of 16 months. Conclusions Clinical management of CKS skin localizations still represents a challenging task for surgeons and oncologists. Therefore, according to this and other author's recent experiences, ECT is claimed to become the "new standard of care" as first line treatment strategy for stage I-II CKS patients. © 2013 Elsevier Ltd. All rights reserved.
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- 2014
75. Pembrolizumab (pembro) plus lenvatinib (len) for first-line treatment of patients (pts) with advanced melanoma: Phase III LEAP-003 study
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H. Kluger, Steven J. O'Day, Matteo S. Carlino, Alexander M.M. Eggermont, Axel Hauschild, B. Homet Moreno, A. Rodgers, Adil Daud, Scott J. Diede, P.A. Ascierto, Alan D. Smith, Matthew H. Taylor, and A. Arance
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Oncology ,medicine.medical_specialty ,Standard of care ,business.industry ,Nci ctcae ,Hematology ,Pembrolizumab ,Health outcomes ,First line treatment ,Clinical trial ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Medicine ,Lenvatinib ,business ,Advanced melanoma - Abstract
Background Pembro, a PD-1 inhibitor, has shown effective antitumor activity, durable responses, and survival benefit in pts with advanced melanoma. Len—a potent inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT—plus a PD-1 inhibitor showed superior antitumor efficacy to either agent alone in a murine tumor model. Len + pembro showed antitumor activity and was well tolerated in pts with advanced melanoma in the phase Ib/II KEYNOTE-146 trial. LEAP-003 will compare the efficacy and safety of pembro ± len in advanced melanoma (NCT03820986). Trial design Eligibility criteria include ≥18 y, histologically/cytologically confirmed unresectable untreated stage III-IV melanoma, documented BRAFV600 status, ECOG performance status 0/1, toxicity resolution from most recent therapy, and provision of baseline tumor sample. Prior first-line standard of care targeted therapy allowed only if pt has BRAFV600-mutant disease. Prior targeted therapy or immunotherapy (as adjuvant/neoadjuvant) allowed if relapse did not occur during treatment or ≤ 6 mo after discontinuation. Pts will be randomized 1:1 to pembro 200 mg every 3 weeks (Q3W) IV plus len 20 mg or placebo QD PO. Randomization will be stratified by BRAF status (mutant/WT), prior adjuvant therapy (PD-1 inhibitor, yes/no), geographic region (China, yes/no). Pembro will continue for up to ∼2 y; len or placebo may continue beyond 2 y in cases of clinical benefit, until progression, unacceptable toxicity, or investigator/pt decision. Response will be assessed per RECIST v1.1 Q9W until wk 54, Q12W until wk 102, and Q24W thereafter. Pts with a CR can discontinue treatment after ≥24 wk of pembro and ≥2 pembro doses after initial CR. Eligible pts can continue treatment beyond initial RECIST-defined PD. AEs will be assessed for ≤90 d and graded per NCI CTCAE v4.0. Survival follow-up will be Q12W. Primary end points are PFS by blinded independent central review (BICR) per modified RECIST v1.1 (max target lesions: 10; 5 per organ) and OS. Secondary end points are ORR and DOR (by BICR per modified RECIST v1.1), safety, and pt-reported health outcomes. Exploratory biomarker and PK analyses of len plus pembro are planned. Clinical trial identification NCT03820986; release date: January 29, 2019. Editorial acknowledgement Doyel Mitra, PhD, CMPP, and Harleigh E. Willmott, PhD, CMPP, of the ApotheCom pembrolizumab team (Yardley, PA, USA). Legal entity responsible for the study Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure A.M.M. Eggermont: Honoraria (self): Actelion, BMS, GSK, Ellipses, Incyte, IO Biotech, IsaPhamaceuticals, MSD, Novartis, Pfizer, Sanofi, Sellas, SkylineDx; Advisory / Consultancy: Actelion, BMS, GSK, Ellipses, Incyte, IO Biotech, IsaPhamaceuticals, MSD, Novartis, Pfizer, Sanofi, Sellas, SkylineDx; Speaker Bureau / Expert testimony: MSD. M.S. Carlino: Honoraria (self): MSD, BMS; Advisory / Consultancy: MSD, BMS, Novartis, Roche, Merck, Pierre Fabre. A. Hauschild: Honoraria (self): Amgen, BMS, MSD/Merck, Novartis, Pierre Fabre, Provectus, Regeneron, Roche, Sanofi-Genzyme; Honoraria (institution), Support for clinical trials: Amgen, BMS, MerckSerono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, Sanofi-Genzyme; Advisory / Consultancy: Amgen, BMS, MerckSerono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, OncoSec, Sanofi-Genzyme, Sun Pharma. P.A. Ascierto: Advisory / Consultancy: BMS, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Genmab, Newlink Genetics, MedImmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC; Research grant / Funding (self): BMS, Roche-Genentech, Array; Travel / Accommodation / Expenses: MSD. A. Arance: Advisory / Consultancy: BMS, MSD, Roche, Novartis, Merck; Travel / Accommodation / Expenses: BMS, MSD, Roche, Novartis, Merck. A. Daud: Advisory / Consultancy: Merck, Pfizer, BMS, Genentech, Incyte, Novartis; Shareholder / Stockholder / Stock options: SQZ; Research grant / Funding (self): BMS, Pfizer, Incyte, Checkmate, Merck. S.J. O’Day: Advisory / Consultancy: Biothera, BMS, Merck, RadImmune, ImaginAB; Speaker Bureau / Expert testimony: BMS; Travel / Accommodation / Expenses: Biothera, BMS, Merck, RadImmune, ImaginAB; Research grant / Funding (institution): Amgen, Biothera, Exicure, Genocea, Incyte, Oncothereapeutics, Ultimovacs, Viralytics. M.H. Taylor: Honoraria (self): BMS, Eisai Inc, Array Biopharma, Arqule, Blueprint Medicines, Bayer, Loxo Oncology, Novartis; Advisory / Consultancy: BMS, Eisai Inc, Array Biopharma, Arqule, Blueprint Medicines, Bayer, Loxo Oncology, Novartis; Speaker Bureau / Expert testimony: BMS, Eisai Inc. A. Smith: Full / Part-time employment: Eisai. A. Rodgers: Full / Part-time employment: Merck & Co., Inc. B. Homet Moreno: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. S.J. Diede: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. H. Kluger: Research grant / Funding (institution): Merck, BMS, Apexigen; Honoraria (self): Regeneron, Alexion, Prometheus, Corvus, Nektar, Biodesix, Roche/Genentech, Pfizer, Iovance, Immunocore, Celldex, Array BioPharma.
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- 2019
76. Predictors of response to checkpoint inhibitors in naïve and ipilimumab-refractory melanoma
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P.A. Ascierto, M. Capone, Sarah Warren, G. Madonna, Domenico Mallardo, Joseph M. Beechem, Alessandra Cesano, and SuFey Ong
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Melanoma ,Ipilimumab ,Hematology ,Immunotherapy ,Pembrolizumab ,Gene signature ,medicine.disease ,Chemotherapy regimen ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,Medicine ,Nivolumab ,business ,medicine.drug - Abstract
Background Response to checkpoint inhibitors (CI) is governed by the tumor immune environment and understanding this immune contexture can predict response. Therapeutic intervention can change this environment even in the absence of clinical response. Patients failing initial immunotherapy may respond to a second line of CI; however, these cohorts show lower overall response rates (ORR). This study identifies transcriptional signatures associated with response to first- and second-line CI monotherapy in melanoma. Methods CI-naive or ipilimumab-refractory patients were treated with ipilimumab, nivolumab or pembrolizumab at the Instituto Nazionale Tumori and clinical response was evaluated by irRECIST 1.1 criteria. Pretreatment tumor biopsies (n = 82) from metastatic lesions were collected and RNA was profiled with the NanoString® IO360 gene expression panel. Results Compared to CI-naive cohorts, ipilimumab-refractory cohorts had reduced ORR to nivolumab (naive: 35%, n = 6; refractory: 20%, n = 10) or pembrolizumab (naive: 67%, n = 6; refractory: 20%, n = 10) with multiple genes differentially expressed between groups. The Tumor Inflammation Signature, an investigational 18 gene signature of suppressed adaptive immune response enriching for pembrolizumab response, was higher in responders versus non-responders in first-line (log2 fold change: 1.56, p = 0.21), but not second-line pembrolizumab (log2 fold change: 0.41, p = 0.60). First-line pembrolizumab responders had elevated MHC2 (log2 fold change: 1.35, p = 0.02) and B cell (log2 fold change: 2.14, p = 0.02) signatures. Upon stratifying the CI-naive cohort between no prior treatment versus prior targeted/chemotherapy, the latter had increased immune expression suggesting these therapies prime the tumor immune environment. Conclusions Correlating patterns of tumor gene expression with clinical response can lead to the development of biomarkers enriching for CI response in both first-line and CI-refractory patients. Utilization of a clinical grade platform such as the NanoString nCounter® may speed the development of diagnostic assays used to predict and monitor patient response to immunotherapy. Legal entity responsible for the study The authors. Funding NanoString Technologies. Disclosure S. Ong: Full / Part-time employment: NanoString Technologies. S. Warren: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. A. Cesano: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. J.M. Beechem: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. P.A. Ascierto: Advisory / Consultancy: Amgen; Advisory / Consultancy: Array; Advisory / Consultancy: BMS; Advisory / Consultancy: Incyte; Advisory / Consultancy: Immunocore; Advisory / Consultancy: MedImmune; Advisory / Consultancy: IDERA; Advisory / Consultancy: Genmab; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Genentech; Advisory / Consultancy: Sandoz; Advisory / Consultancy: Syndax; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Ultimovacs; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Novartis. All other authors have declared no conflicts of interest.
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- 2019
77. Significant differences in outcome between Immunoscore categories in stage I colon cancer patients
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A. Hartmann, Toshihiko Torigoe, Bernard A. Fox, Jérôme Galon, Pamela S. Ohashi, Francesco M. Marincola, Franck Pages, Alessandro Lugli, Carlo Bifulco, Fabienne Hermitte, M. Van den Eynde, P.A. Ascierto, F. Marliot, Michael H.A. Roehrl, Yi Wang, P. Patel, Yutaka Kawakami, Eva Zavadova, Bernhard Mlecnik, and Iris D. Nagtegaal
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Oncology ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Internal medicine ,medicine ,Hematology ,medicine.disease ,business ,Outcome (game theory) - Published
- 2019
78. An analysis of nivolumab-mediated adverse events and association with clinical efficacy in resected stage III or IV melanoma (CheckMate 238)
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Larkin Jmg., P.A. Ascierto, Michael Millward, Maurice Lobo, J.-J. Grob, Jeffrey S. Weber, M. Del Vecchio, Jose Lutzky, Marcus O. Butler, Fernandez Ama., V. de Pril, Helen Gogas, Ivan Marquez-Rodas, Mario Mandalà, Michael Schenker, A.M. Di Giacomo, Charles Lance Cowey, S. Dalle, Mark R. Middleton, and V. Chiarion-Sileni
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Melanoma ,Checkmate ,Ipilimumab ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In patient ,Clinical efficacy ,Nivolumab ,Stage (cooking) ,business ,Adverse effect ,030215 immunology ,medicine.drug - Abstract
9584 Background: In both previous 18- and 24-month follow-up reports from CheckMate 238, NIVO demonstrated significantly longer recurrence-free survival (RFS) than ipilimumab (IPI) in patients (pts) with resected stage IIIB/C or stage IV melanoma. Here we provide a more comprehensive analysis of treatment-related adverse events (TRAEs) for NIVO over discrete follow-up intervals and an investigation of the association of these AEs with efficacy (RFS). Methods: Eligible pts were aged ≥15 years and underwent complete resection of stage IIIB/C or IV melanoma. A total of 453 pts were treated with NIVO 3 mg/kg Q2W for up to 1 year. The primary endpoint was RFS. Pts were followed for safety for up to 100 days following their last dose; as of the previous 18-month database lock, all pts had been off study drug for > 100 days. Here safety data were analyzed within discrete time intervals: months 0–3 of treatment (0–3), months 3–12 of treatment (3–12), and from last dose to 100 days after last dose (+100). In addition, the association of TRAEs with RFS was investigated using the 24-month efficacy dataset, accounting for time-delay bias within the first 12 weeks after randomization. Results: The incidence of the first onset of TRAEs reported in ≥5% of pts was highest in the 0–3 time frame; the most common TRAEs with NIVO were fatigue (28% for 0–3 vs 6% for 3–12 vs 2% for +100), pruritus (16% vs 7% vs 1%), and diarrhea (15% vs 7% vs 2%). Most TRAEs with NIVO resolved within 3 months of occurrence, except for endocrine AEs, which could have required hormone supplementation, and skin AEs (median overall resolution time of 48 and 22 weeks, respectively). Similar results were observed in an analysis taking into account repeat occurrences of TRAEs over time. Analyses investigating the association of TRAEs with RFS are ongoing and will be presented. Conclusions: These results in pts with resected stage IIIB/C or IV melanoma are consistent with the established safety profile of NIVO. Based on the time periods analyzed, the majority of TRAEs with adjuvant NIVO occurred early during treatment, and patients had a reduced frequency of TRAEs after the treatment course. The majority of select TRAEs resolved within 3 months. Clinical trial information: NCT02388906.
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- 2019
79. Electrochemotherapy in melanoma: a European e-Delphi survey to define a consensus on indications, treatment modalities and quality indicators
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J. Hafner, Erika Kis, S. Farronato, Christian Kunte, M. Bourke, G. Gerlini, K. Eisendle, Falk G. Bechara, Gregor Sersa, Roberto Patuzzo, M. Mühlstädt, P.A. Ascierto, Antonio Orlando, Matteo Brizio, Roberto Marconato, L.G. Campana, Sara Valpione, J. Clover, Pietro Quaglino, and Corrado Caracò
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Electrochemotherapy ,medicine.medical_specialty ,business.industry ,Melanoma ,media_common.quotation_subject ,Delphi method ,General Medicine ,medicine.disease ,Oncology ,Treatment modality ,Medicine ,Surgery ,Quality (business) ,Medical physics ,business ,media_common - Published
- 2019
80. Avelumab in European patients (pts) with metastatic Merkel cell carcinoma (mMCC): Experience from an ad hoc expanded access program (EAP)
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P.A. Ascierto, P. Nathan, V. Kasturi, L.Y. Dirix, E. Fenig, M. Hennessy, J. Reed, A. Engelsberg, S. Hariharan, and C. Lebbe
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Oncology ,Hematology - Published
- 2018
81. Traitement adjuvant par nivolumab (NIVO) par rapport à l’ipilimumab (IPI) après résection complète d’un mélanome au stade III/IV : résultats actualisés d’un essai de phase III (CheckMate 238)
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J.-J. Grob, Michael Schenker, J.M.G. Larkin, P.A. Ascierto, M. Del Vecchio, Mario Mandalà, Helen Gogas, Ivan Marquez-Rodas, V. Atkinson, S. Dalle, C. Lance Cowey, Anila Qureshi, J.S. Weber, Michele Maio, Marcus O. Butler, Ana Arance, V. de Pril, Mark R. Middleton, V. Chiarion-Sileni, and R. Dummer
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Dermatology - Abstract
Introduction Dans le rapport initial des donnees de l’essai CheckMate 238, apres un suivi minimal de 18 mois, le NIVO demontrait une survie sans recidive (SSR) significativement plus longue par rapport a l’IPI chez des patients (pts) atteints d’un melanome au stade III ou IV reseque. Nous rapportons ici les resultats d’efficacite mis a jour de cette etude de phase III, apres un suivi de 6 mois supplementaires. Patients et methodes Les pts eligibles avaient plus de 15 ans et avaient eu une resection complete d’un melanome au stade IIIB/C ou IV ; 906 pts ont ete randomises selon un rapport de 1 : 1 (stratifies en fonction du stade de la maladie et du statut PD-L1 a un seuil de 5 %) pour recevoir du NIVO a raison de 3 mg/kg 1 × /2 sem (n = 453) ou de l’IPI a raison de 10 mg/kg 1 × /3 sem pendant 4 doses, puis 1 × /12 sem (a compter de la semaine 24) (n = 453) pour une duree maximale d’un an ou jusqu’a la recidive de la maladie ou une toxicite inacceptable. Le critere d’evaluation principal etait la SSR ; la survie sans metastases distantes (SSMD) chez les pts atteints de la maladie au stade III etait un critere d’evaluation exploratoire. Resultats Apres un suivi minimal de 24 mois, la SSR continuait d’etre significativement plus longue avec le NIVO par rapport a l’IPI (risque relatif de 0,66, p Tableau 1 ). La SSMD a egalement continue d’etre significativement plus longue pour le NIVO que pour l’IPI, avec des taux a 24 mois de 70,5 % et 63,7 %, respectivement (risque relatif de 0,76, p = 0,034). Des traitements ulterieurs ont ete recus par 31,1 % des pts dans le groupe NIVO et 41,1 % dans le groupe IPI. Conformement au protocole, il n’y a pas eu d’evaluation supplementaire de la tolerance pour l’analyse actuelle etant donne que les patients n’etaient plus sous traitement depuis > 100 jours au moment de la precedente date limite de recueil des donnees. Conclusion Avec un suivi prolonge, le NIVO a demontre un benefice en termes d’efficacite durable par rapport a l’IPI chez des pts atteints d’un melanome au stade III/IV reseque a risque eleve de recidive, independamment du stade de la maladie, de l’expression de PD-L1, ou du statut mutationnel BRAF.
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- 2018
82. EP-1396: Radiosurgery/Stereotacticradiotherapy with Cyberknife and immunotherapy in melanoma brain metastases
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P.A. Ascierto, V. Borzillo, Fabrizio Cammarota, Anna Grimaldi, R. Di Franco, Vincenzo Ravo, Giuseppe Totaro, Sara Falivene, and Paolo Muto
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Melanoma ,Immunotherapy ,Hematology ,medicine.disease ,Radiosurgery ,Cyberknife ,Radiology Nuclear Medicine and imaging ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,business - Published
- 2016
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83. Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: results of a phase I dose escalation study
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P.A. Ascierto, Jamila Louahed, Ralf Gutzmer, Dirk Schadendorf, Lev V. Demidov, Armando Santoro, N. Vanhoutte, Jochen Utikal, Carmen Loquai, P M De Sousa Alves, Paola Queirolo, Frederic Lehmann, Axel Hauschild, B. Dréno, V G Brichard, Marc Gillet, Erwin S. Schultz, B. Salaun, Jean-Jacques Grob, Licia Rivoltini, Thierry Lesimple, Silvija Jarnjak, Ruggero Ridolfi, Alberto Testori, Evgeny Levchenko, Skin Cancer Center Hannover, Hannover Medical School [Hannover] (MHH), Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori-IRCCS Foundation, Petrov Research Insitut of Oncology, Division of Melanoma and Muscolocutaneous sarcoma, European Institute of Oncology, Skin Cancer Unit of the German Cancer Research Center Heidelberg, University Mannheim, Istituto Nazionale per lo studio e la cura dei Tumori, Naples, Italy, Cancer Research Center, Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Immunoterapia e Terapia Cellulare Somatica, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Department of Dermatology, University Hospital Essen, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Johannes Gutenberg - Universität Mainz (JGU), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Schleswig-Holstein University Hospitals, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Surgical oncology Centre Eugènes Marquis, Centre Eugènes Marquis, GSK Vaccines - Belgium, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Bernardo, Elizabeth, and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
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safety ,Cancer Research ,medicine.drug_class ,medicine.medical_treatment ,Medizin ,Phases of clinical research ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,immunogenicity ,Immunostimulant ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cancer immunotherapy ,medicine ,030304 developmental biology ,Original Research ,PRAME antigen ,0303 health sciences ,PRAME ,cancer immunotherapy ,business.industry ,Melanoma ,Immunogenicity ,Cancer ,medicine.disease ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Chills ,medicine.symptom ,business ,metastatic melanoma - Abstract
Purpose The PRAME tumour antigen is expressed in several tumour types but in few normal adult tissues. A dose-escalation phase I/II study (NCT01149343) assessed the safety, immunogenicity and clinical activity of the PRAME immunotherapeutic (recombinant PRAME protein (recPRAME) with the AS15 immunostimulant) in patients with advanced melanoma. Here, we report the phase I dose-escalation study segment. Patients and methods Patients with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 intramuscular injections of the PRAME immunotherapeutic. The RecPRAME dose was 20, 100 or 500 µg in cohorts 1, 2 and 3, respectively, with a fixed dose of AS15. Adverse events (AEs), including predefined dose-limiting toxicity (DLT) and the anti-PRAME humoral response (ELISA), were coprimary end points. Cellular immune responses were evaluated using in vitro assays. Results 66 patients were treated (20, 24 and 22 in the respective cohorts). AEs considered by the investigator to be causally related were mostly grade 1 or 2 injection site symptoms, fatigue, chills, fever and headache. Two DLTs (grade 3 brain oedema and proteinuria) were recorded in two patients in two cohorts (cohorts 2 and 3). All patients had detectable anti-PRAME antibodies after four immunisations. Percentages of patients with predefined PRAME-specific-CD4+T-cell responses after four immunisations were similar in each cohort. No CD8+ T-cell responses were detected. Conclusions The PRAME immunotherapeutic had an acceptable safety profile and induced similar anti-PRAME-specific humoral and cellular immune responses in all cohorts. As per protocol, the phase II study segment was initiated to further evaluate the 500 µg PRAME immunotherapeutic dose. Trial registration number NCT01149343, Results.
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- 2016
84. Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab
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Sara Gandini, P.A. Ascierto, Pier Francesco Ferrucci, Sara Valpione, Ester Simeone, Francesco Spagnolo, Emilia Cocorocchio, Maresa Altomonte, Diana Giannarelli, Mario Mandalà, Paola Savoia, Paola Queirolo, G. C.Antonini Cappellini, Chiara Martinoli, Michele Maio, Jacopo Pigozzo, M. Del Vecchio, and Massimo Guidoboni
- Subjects
Male ,0301 basic medicine ,Oncology ,Neutrophils ,Lymphocyte ,Biomarker ,dNLR ,Ipilimumab ,Melanoma ,Neutrophil ,Prognosis ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Lymphocytes ,Aged, 80 and over ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,medicine.anatomical_structure ,Italy ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Metastatic melanoma ,Adolescent ,Subgroup analysis ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Lymphocyte Count ,Neutrophil to lymphocyte ratio ,Aged ,Receiver operating characteristic ,business.industry ,medicine.disease ,030104 developmental biology ,Expanded access ,business - Abstract
Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need.Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access program were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cutoff for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also carried out.The median follow-up was 16.5 months. The optimal cutoff for dNLR was 3. Baseline ANC and dNLR were significantly associated with the outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P0.0001 for all). Furthermore, for each elevated variable, prognosis worsened. Patients with both ANC ≥ 7500 and dNLR ≥ 3 had a significantly and independently increased risk of death [hazard ratio(HR) = 5.76; 95% confidence interval (CI) 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1- and 2-year survival rates were 2% and 0%, respectively, for patients with ANC ≥ 7500 and dNLR ≥ 3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR.Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease-management strategies. Furthermore, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials.
- Published
- 2016
85. BRIM8: a randomized, double-blind, placebo-controlled study of adjuvant vemurafenib in patients (pts) with completely resected, BRAFV600+ melanoma at high risk for recurrence
- Author
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Andrzej Mackiewicz, Alexander Guminski, P.A. Ascierto, Grant R. Goodman, Lev V. Demidov, B. Simmons, C. Ye, Yibing Yan, Piotr Rutkowski, Mario Mandalà, C. Herbert, Dirk Schadendorf, Karl D. Lewis, and Michele Maio
- Subjects
0301 basic medicine ,Brachial Plexus Neuritis ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Melanoma ,Placebo-controlled study ,Hematology ,medicine.disease ,Surgery ,Double blind ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,In patient ,business ,Vemurafenib ,Adjuvant ,medicine.drug - Published
- 2017
86. Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: A randomized, double-blind, phase 3 trial (CheckMate 238)
- Author
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Anila Qureshi, Victoria Atkinson, V. Chiarion-Sileni, Helen Gogas, Ana Arance, V. de Pril, Jeffrey S. Weber, P.A. Ascierto, Michael Schenker, M. Del Vecchio, Stéphane Dalle, J.M.G. Larkin, Ivan Marquez-Rodas, L.C. Cowey, Mario Mandalà, J.-J. Grob, Paola Queirolo, Mark R. Middleton, Michele Maio, and Mark S. Butler
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Melanoma ,Checkmate ,Ipilimumab ,Hematology ,030204 cardiovascular system & hematology ,medicine.disease ,Complete resection ,Double blind ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Adjuvant therapy ,Medicine ,Stage (cooking) ,Nivolumab ,business ,030217 neurology & neurosurgery ,medicine.drug - Published
- 2017
87. Nivolumab (NIVO) in patients (pts) with advanced (adv) chemotherapy-refractory (CT-Rx) esophagogastric (EG) cancer according to microsatellite instability (MSI) status: checkmate 032
- Author
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Christopher T. Harbison, Ian Chau, Dung T. Le, P.A. Ascierto, Johanna C. Bendell, Dirk Jäger, Huanyu Zhao, Padmanee Sharma, Katriina Peltola, Yelena Y. Janjigian, F. de Braud, Patrick A. Ott, Emiliano Calvo, T.R.J. Evans, Joseph Kim, Marina Tschaika, and Petri Bono
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Chemotherapy ,030102 biochemistry & molecular biology ,business.industry ,medicine.medical_treatment ,Checkmate ,Cancer ,Microsatellite instability ,Hematology ,medicine.disease ,03 medical and health sciences ,Refractory ,Internal medicine ,Medicine ,In patient ,business - Published
- 2017
88. PO-0741: Ipilimumab and stereotactic radiosurgery with cyberknife in melanoma brain metastases
- Author
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Anna Grimaldi, R. Di Franco, Ester Simeone, Sara Falivene, Fabrizio Cammarota, Francesca Maria Giugliano, A. Martino, Vito Vanella, Lucia Festino, V. Borzillo, Paolo Muto, Diana Giannarelli, Vincenzo Ravo, P.A. Ascierto, and Giuseppe Totaro
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Melanoma ,Ipilimumab ,Hematology ,medicine.disease ,Radiosurgery ,Oncology ,Cyberknife ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,medicine.drug - Published
- 2017
89. Nivolumab (N) alone or in combination with ipilimumab (I) in patients (pts) with platinum-pretreated metastatic urothelial carcinoma (mUC), including the nivolumab 1 mg/kg + ipilimumab 3 mg/kg expansion from CheckMate 032
- Author
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Emiliano Calvo, Margaret K. Callahan, P.A. Ascierto, Peter Brossart, Kristoffer Staal Rohrberg, Jonathan E. Rosenberg, Michael A. Morse, Wen Hong Lin, Abdel Saci, Padmanee Sharma, Noemi Reguart, Umberto Basso, S. Meadows-Shropshire, F. de Braud, Arlene O. Siefker-Radtke, Jose A. Lopez-Martin, and Petri Bono
- Subjects
0301 basic medicine ,Oncology ,Brachial Plexus Neuritis ,medicine.medical_specialty ,Metastatic Urothelial Carcinoma ,CARCINOMA TRANSITIONAL CELL ,business.industry ,Ipilimumab ,Hematology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,In patient ,Nivolumab ,business ,medicine.drug - Published
- 2018
90. KEYNOTE-022 Part 3: Phase II randomized study of 1L dabrafenib (D) and trametinib (T) plus pembrolizumab (Pembro) or placebo (PBO) for BRAF-mutant advanced melanoma
- Author
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Rosalie Stephens, Razi Ghori, Michal Lotem, Gil Bar-Sela, Victoria Atkinson, A.M. Di Giacomo, Antoni Ribas, Nageatte Ibrahim, Félix Couture, P.A. Ascierto, Henrik Schmidt, Jacob Schachter, Georgina V. Long, Bijoyesh Mookerjee, Pier Francesco Ferrucci, Paola Queirolo, Inge Marie Svane, M. Del Vecchio, and B. Homet Moreno
- Subjects
0301 basic medicine ,Oncology ,Trametinib ,medicine.medical_specialty ,business.industry ,Melanoma ,Mutant ,Dabrafenib ,Hematology ,Pembrolizumab ,Placebo ,medicine.disease ,law.invention ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,medicine.drug ,Advanced melanoma - Published
- 2018
91. Health-related quality-of-life results for pembrolizumab versus placebo after complete resection of high-risk stage III melanoma from the EORTC 1325-MG/Keynote 054 trial: An international randomized double-blind phase III trial
- Author
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James Larkin, Mario Mandalà, Andrew Haydon, Stéphane Dalle, Adnan Khattak, P.A. Ascierto, Matteo S. Carlino, Dirk Schadendorf, Corneel Coens, Victoria Atkinson, Andrew Bottomley, Christian U. Blank, Georgina V. Long, C. Robert, Alexander M.M. Eggermont, Stefan Suciu, S. Puig Sarda, Shahneen Sandhu, Mikhail Lichinitser, and Nageatte Ibrahim
- Subjects
0301 basic medicine ,Oncology ,Health related quality of life ,medicine.medical_specialty ,business.industry ,Medizin ,Hematology ,Pembrolizumab ,Placebo ,Complete resection ,Double blind ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Quality of life ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Stage III melanoma ,Melanoma stage iii ,business - Published
- 2018
92. Avelumab in European patients (pts) with metastatic Merkel cell carcinoma (mMCC): Experience from an ad-hoc expanded access program (EAP)
- Author
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Meliessa Hennessy, C. Lebbé, Subramanian Hariharan, Paul Nathan, Arne Engelsberg, Luc Dirix, Eyal Fenig, Vijay Kasturi, P.A. Ascierto, and Josh Reed
- Subjects
Oncology ,Brachial Plexus Neuritis ,medicine.medical_specialty ,Merkel cell carcinoma ,business.industry ,Hematology ,medicine.disease ,Avelumab ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Expanded access ,medicine ,business ,030215 immunology ,medicine.drug - Published
- 2018
93. Initial results from a phase IIIb/IV study evaluating two dosing regimens of nivolumab (NIVO) in combination with ipilimumab (IPI) in patients with advanced melanoma (CheckMate 511)
- Author
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C. Lebbé, Elena Grigoryeva, Ivan Marquez-Rodas, Laurent Mortier, C. Robert, A.M. Menzies, P.A. Ascierto, Michael Smylie, Piotr Rutkowski, Inge Marie Svane, Abdel Saci, Ricardo J. Gonzalez, Linda Rollin, Jacopo Pigozzo, Thomas Eigentler, Mazhar Ajaz, and Nicolas Meyer
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Melanoma ,Checkmate ,Ipilimumab ,Hematology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In patient ,Dosing ,Nivolumab ,business ,Advanced melanoma ,medicine.drug - Published
- 2018
94. Preoperative nivolumab in patients(pts) with locally advanced colon cancer (T3 or T4): A window-of-opportunity study (NICOLE)
- Author
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Paolo Delrio, Lucrezia Silvestro, Guglielmo Nasti, A. Cassata, Secondo Lastoria, Ernesta Cavalcanti, Anna Nappi, Fabiana Tatangelo, Carmela Romano, P.A. Ascierto, A. De Stefano, Alfredo Budillon, Rossana Casaretti, Alessandro Ottaiano, Jérôme Galon, Piera Maiolino, Antonella Petrillo, E. Di Gennaro, A. Avallone, and Diana Giannarelli
- Subjects
Oncology ,medicine.medical_specialty ,Window of opportunity ,business.industry ,Colorectal cancer ,Locally advanced ,Hematology ,medicine.disease ,Internal medicine ,Medicine ,In patient ,Nivolumab ,business - Published
- 2018
95. A randomized, open-label, phase II open platform study evaluating the efficacy and safety of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma (PLATForM)
- Author
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Paul Nathan, Dirk Schadendorf, Eduard Gasal, P.A. Ascierto, A. Ribas, Aislyn Boran, R. Dummer, J.B.A.G. Haanen, Jeffrey S. Weber, Georgina V. Long, C. Robert, A. Arance, Bettinger S, and Anthony D'Amelio
- Subjects
Oncology ,medicine.medical_specialty ,Open platform ,Metastatic melanoma ,business.industry ,Internal medicine ,Medizin ,medicine ,Hematology ,Open label ,Previously treated ,business - Published
- 2018
96. Immuno-related adverse events from check-point inhibitors during immune-therapy for cancer. Imaging findings
- Author
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P.A. Ascierto, S. Pizza, Ester Simeone, S. V. Setola, Onofrio A. Catalano, Fabio Sandomenico, Angelica Petrillo, Lucia Festino, Vito Vanella, Anna Grimaldi, and G. De Rosa
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,Immunotherapy ,Cancer imaging ,medicine.disease ,Internal medicine ,medicine ,Adverse effect ,business ,Check point - Abstract
Poster: "ECR 2018 / C-2079 / Immuno-related adverse events (irAE) from check-Point inhibitors during immunotherapy for cancer. Imaging Findings." by: "F. Sandomenico1, S. Pizza2, G. De Rosa1, O. Catalano3, E. simeone1, L. festino1, A. M. grimaldi1, P. Ascierto3, A. Petrillo3; 1Napoli/IT, 2Napoli (NA)/IT, 3Naples/IT"
- Published
- 2018
97. Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study
- Author
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Ester Fonsatti, P.A. Ascierto, M. Del Vecchio, A. Testori, Giorgio Parmiani, Ester Simeone, Michele Maio, Diana Giannarelli, Massimo Guidoboni, Riccardo Danielli, Mario Santinami, A.M. Di Giacomo, Lorenzo Pilla, Andrea Maurichi, Ruggero Ridolfi, Paola Queirolo, Luana Calabrò, L. Orgiano, Giuseppe Spadola, Cristina Maccalli, and Diego Annesi
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Skin Neoplasms ,Lymphocyte ,medicine.medical_treatment ,Ipilimumab ,Metastatic melanoma ,Asymptomatic ,Nitrosourea Compounds ,NO ,Organophosphorus Compounds ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,CTLA-4 ,Fotemustine ,Immunotherapy ,Adverse effect ,Melanoma ,Aged ,Neoplasm Staging ,Brain Neoplasms ,business.industry ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,Prognosis ,Confidence interval ,Surgery ,Biological Therapy ,Survival Rate ,Radiation therapy ,medicine.anatomical_structure ,Population study ,Female ,medicine.symptom ,business ,Follow-Up Studies ,medicine.drug - Abstract
Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of the combination of ipilimumab and fotemustine in metastatic melanoma patients with or without brain metastases. The addition of fotemustine to ipilimumab does not impair its immunomodulatory activity. Background In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. Patients and methods This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3+CD4+ICOS+CD45RO+ or CD45RA+ T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. Results Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1–18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7–22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in ‘memory’ but not in ‘naive’ T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points.BRAF status did not correlate with clinical outcome. Conclusions Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab. EudraCT number 2010-019356-50. CinicalTrials.gov NCT01654692.
- Published
- 2015
98. Efficacy and safety of single agent pan-HER inhibitor Dacomitinib in the treatment of unresectable or metastatic skin squamous cell cancer - Trial in progress
- Author
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Paolo Bossi, F. Favales, P.A. Ascierto, Lisa Licitra, and Marco Palla
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,business.industry ,Skin squamous cell cancer ,Hematology ,Dacomitinib ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,Single agent ,business - Published
- 2015
99. EP-1392: The abscopal effect:efficacy of radiotherapy in patients on progression after ipilimumab 3 mg/kg
- Author
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Anna Grimaldi, P.A. Ascierto, Antonella Petrillo, G. Ciliberto, M. Palla, Fabio Sandomenico, Diana Giannarelli, Sara Falivene, M. Paone, Nicola Mozzillo, M. Curvietto, G. Palmieri, Paolo Muto, Antonella Esposito, Francesca Maria Giugliano, V. Borzillo, Ester Simeone, and Corrado Caracò
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Abscopal effect ,Ipilimumab ,Hematology ,Radiation therapy ,Radiology Nuclear Medicine and imaging ,Internal medicine ,Medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,business ,medicine.drug - Published
- 2016
100. Adjuvant therapy of melanoma: what's new?
- Author
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P.A. Ascierto, M. T. Melucci, Antonio Daponte, R. A. Satriano, Giuseppe Palmieri, Giuseppe Castello, and Nicola Mozzillo
- Subjects
Risk ,Oncology ,Cancer Research ,medicine.medical_specialty ,Immunologic Factors ,Alpha interferon ,Dermatology ,Adjuvant therapy ,Disease-Free Survival ,Text mining ,Internal medicine ,melanoma ,medicine ,Humans ,Multicenter Studies as Topic ,Combined Modality Therapy ,neoplasms ,Survival analysis ,Randomized Controlled Trials as Topic ,Clinical Trials as Topic ,business.industry ,Melanoma ,Follow up studies ,Interferon-alpha ,medicine.disease ,Survival Analysis ,Treatment Outcome ,Clinical Trials, Phase III as Topic ,Chemotherapy, Adjuvant ,Lymph Node Excision ,business ,Follow-Up Studies - Abstract
Adjuvant therapy of melanoma
- Published
- 2002
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