Journal ArticleDOI
Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial
Luana Calabrò,Aldo Morra,Ester Fonsatti,Ornella Cutaia,Giovanni Amato,Diana Giannarelli,Anna Maria Di Giacomo,Riccardo Danielli,Maresa Altomonte,Luciano Mutti,Michele Maio +10 more
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TLDR
Although the effect size was small in the phase 2 trial, tremelimumab seemed to have encouraging clinical activity and an acceptable safety and tolerability profile in previously treated patients with advanced malignant mesothelioma.Abstract:
Summary Background Monoclonal antibodies to cytotoxic T-lymphocyte antigen 4 (CTLA4) have therapeutic activity in different tumour types. We aimed to investigate the efficacy, safety, and immunological activity of the anti-CTLA4 monoclonal antibody, tremelimumab, in advanced malignant mesothelioma. Methods In our open-label, single-arm, phase 2 study, we enrolled patients aged 18 years or older with measurable, unresectable malignant mesothelioma and progressive disease after a first-line platinum-based regimen. Eligible patients had to have a life expectancy of 3 months or more, an Eastern Cooperative Oncology Group performance status of 2 or less, and no history of autoimmune disease. Patients received tremelimumab 15 mg/kg intravenously once every 90 days until progressive disease or severe toxicity. The primary endpoint was the proportion of patients who achieved an objective response (complete or partial response), with a target response rate of 17% according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) for pleural malignant mesothelioma or standard RECIST 1.0 for peritoneal malignant mesothelioma. Analyses were done according to intention to treat. This trial is registered with EudraCT, number 2008-005171-95, and ClinicalTrials.gov, number NCT01649024. Findings Between May 27, 2009, and Jan 10, 2012, we enrolled 29 patients. All patients received at least one dose of tremelimumab (median two doses, range one to nine). No patients had a complete response and two patients (7%) had a durable partial response (one lasting 6 months and one lasting 18 months); one partial response occurred after initial progressive disease. Thus, the study did not reach its primary endpoint. However, we noted disease control in nine (31%) patients and a median progression-free survival of 6·2 months (95% CI 1·3–11·1) and a median overall survival of 10·7 months (0·0–21·9). 27 patients (93%) had at least one grade 1–2 treatment-emergent adverse event (mainly cutaneous rash, pruritus, colitis, or diarrhoea), and four patients (14%) had at least one grade 3–4 treatment-emergent adverse event (two gastrointestinal, one neurological, two hepatic, and one pancreatic). Interpretation Although the effect size was small in our phase 2 trial, tremelimumab seemed to have encouraging clinical activity and an acceptable safety and tolerability profile in previously treated patients with advanced malignant mesothelioma. Funding Associazione Italiana per la Ricerca sul Cancro, Istituto Toscano Tumori, Pfizer, and Fondazione Buzzi Unicem.read more
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References
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Journal ArticleDOI
Advances in Malignant Mesothelioma
TL;DR: The authors review advances made in the past 5 to 10 years in the understanding, diagnosis, and management of mesothelioma.
Journal ArticleDOI
Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non–Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study
Thomas J. Lynch,Igor Bondarenko,Alexander Luft,Piotr Serwatowski,Fabrice Barlesi,Raju Titus Chacko,Martin Sebastian,Joel W. Neal,Haolan Lu,Jean-Marie Cuillerot,Martin Reck +10 more
TL;DR: Phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS, which supports additional investigation of ipil optimumab in NSCLC.
Journal ArticleDOI
Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma
Antoni Ribas,Richard F. Kefford,Margaret A. Marshall,Cornelis J. A. Punt,John B. A. G. Haanen,Maribel Marmol,Claus Garbe,Helen Gogas,Jacob Schachter,Gerald P. Linette,Paul Lorigan,Kari Kendra,Michele Maio,Uwe Trefzer,Michael Smylie,Grant A. McArthur,Brigitte Dréno,Paul Nathan,Jacek Mackiewicz,John M. Kirkwood,Jesus Gomez-Navarro,Bo Huang,Dmitri Pavlov,Axel Hauschild +23 more
TL;DR: In this article, the authors evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy.
Journal ArticleDOI
Modified RECIST criteria for assessment of response in malignant pleural mesothelioma
TL;DR: These Modified RECIST criteria for tumour response correlate with survival and lung function and can be used to measure outcome in pleural mesothelioma.
Journal ArticleDOI
Prognostic factors in patients with pleural mesothelioma : The European Organization for Research and Treatment of Cancer Experience
Desmond Curran,Tarek Sahmoud,Patrick Therasse,J. Van Meerbeeck,Pieter E. Postmus,G. Giaccone +5 more
TL;DR: Identification of prognostic factors in patients with malignant pleural mesothelioma based on prospectively collected international data may help to design new clinical trials in pleural Mesot Helioma by selecting more homogenous groups of patients.
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