Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial
Arnaud Scherpereel,Julien Mazieres,Laurent Greillier,Sylvie Lantuejoul,Pascal Do,O. Bylicki,Isabelle Monnet,Romain Corre,Clarisse Audigier-Valette,M. Locatelli-Sanchez,Olivier Molinier,Florian Guisier,Thierry Urban,Catherine Ligeza-poisson,David Planchard,E. Amour,Franck Morin,Denis Moro-Sibilot,Gérard Zalcman,Didier Debieuvre,Sandrine Hiret,Jacques Cadranel,Séverine Fraboulet-Moreau,Delphine Carmier +23 more
TLDR
This multicentre randomised, non-comparative, open-label, phase 2 trial aimed to prospectively assess the anti-PD-1 monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma.Abstract:
Summary Background There is no recommended therapy for malignant pleural mesothelioma that has progressed after first-line pemetrexed and platinum-based chemotherapy. Disease control has been less than 30% in all previous studies of second-line drugs. Preliminary results have suggested that anti-programmed cell death 1 (PD-1) monoclonal antibody could be efficacious in these patients. We thus aimed to prospectively assess the anti-PD-1 monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma. Methods This multicentre randomised, non-comparative, open-label, phase 2 trial was done at 21 hospitals in France. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1, histologically proven malignant pleural mesothelioma progressing after first-line or second-line pemetrexed and platinum-based treatments, measurable disease by CT, and life expectancy greater than 12 weeks. Patients were randomly allocated (1:1) to receive intravenous nivolumab (3 mg/kg bodyweight) every 2 weeks, or intravenous nivolumab (3 mg/kg every 2 weeks) plus intravenous ipilimumab (1 mg/kg every 6 weeks), given until progression or unacceptable toxicity. Central randomisation was stratified by histology (epithelioid vs non-epithelioid), treatment line (second line vs third line), and chemosensitivity to previous treatment (progression ≥3 months vs Findings Between March 24 and August 25, 2016, 125 eligible patients were recruited and assigned to either nivolumab (n=63) or nivolumab plus ipilimumab (n=62). In the first 108 eligible patients, 12-week disease control was achieved by 24 (44%; 95% CI 31–58) of 54 patients in the nivolumab group and 27 (50%; 37–63) of 54 patients in the nivolumab plus ipilimumab group. In the intention-to-treat population, 12-week disease control was achieved by 25 (40%; 28–52) of 63 patients in the nivolumab group and 32 (52%; 39–64) of 62 patients in the combination group. Nine (14%) of 63 patients in the nivolumab group and 16 (26%) of 61 patients in the combination group had grade 3–4 toxicities. The most frequent grade 3 adverse events were asthenia (one [2%] in the nivolumab group vs three [5%] in the combination group), asymptomatic increase in aspartate aminotransferase or alanine aminotransferase (none vs four [7%] of each), and asymptomatic lipase increase (two [3%] vs one [2%]). No patients had toxicities leading to death in the nivolumab group, whereas three (5%) of 62 in the combination group did (one fulminant hepatitis, one encephalitis, and one acute kidney failure). Interpretation Anti-PD-1 nivolumab monotherapy or nivolumab plus anti-CTLA-4 ipilimumab combination therapy both showed promising activity in relapsed patients with malignant pleural mesothelioma, without unexpected toxicity. These regimens require confirmation in larger clinical trials. Funding French Cooperative Thoracic Intergroup.read more
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First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial.
Paul Baas,Arnaud Scherpereel,Anna K. Nowak,Nobukazu Fujimoto,Solange Peters,Anne S. Tsao,Aaron S. Mansfield,Sanjay Popat,Thierry Jahan,Scott J. Antonia,Youssef Oulkhouir,Yolanda Bautista,Robin Cornelissen,Laurent Greillier,Francesco Grossi,Dariusz M. Kowalski,Jerónimo Rodríguez-Cid,Praveen Aanur,Abderrahim Oukessou,Christine Baudelet,Gérard Zalcman +20 more
TL;DR: The CheckMate 743 trial as mentioned in this paper showed that nivolumab plus ipilimumab significantly improved overall survival compared to standard-of-care chemotherapy for non-small-cell lung cancer.
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Combination of CTLA-4 and PD-1 blockers for treatment of cancer
TL;DR: This review aims to support future research in combination immunotherapy by discussing the basic details of CTLA-4 and PD-1 pathways and the results from clinical studies that evaluated combination of CT LA4 andPD-1/PD-L1 blockers.
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The Next Decade of Immune Checkpoint Therapy.
Padmanee Sharma,Bilal A. Siddiqui,Swetha Anandhan,Shalini S. Yadav,Sumit K. Subudhi,Jianjun Gao,Sangeeta Goswami,James P. Allison +7 more
TL;DR: In this article, the authors survey the current understanding of mechanisms of response and resistance to ICT and propose a path forward to improving efficacy and minimizing toxicities through better patient selection and rational combinations.
Journal ArticleDOI
Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial.
Maria J. Disselhorst,Josine Quispel-Janssen,Ferry Lalezari,Kim Monkhorst,Jeltje F. de Vries,Vincent van der Noort,Emmy Harms,Sjaak Burgers,Paul Baas +8 more
TL;DR: In this single-centre phase 2 trial, the combination of nivolumab plus ipilimumab showed marked efficacy in patients with recurrent malignant pleural mesothelioma and the safety profile was consistent with known data on the combination regimen.
Journal ArticleDOI
A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial
Sanjay Popat,Alessandra Curioni-Fontecedro,Urania Dafni,R. Shah,Mary O'Brien,A. Pope,Patricia Fisher,James Spicer,Arup Roy,David Gilligan,Oliver Gautschi,E. Nadal,W.-D. Janthur,R. López Castro,R. García Campelo,S. Rusakiewicz,Igor Letovanec,Varvara Polydoropoulou,H. Roschitzki-Voser,Barbara Ruepp,A. Gasca-Ruchti,Solange Peters,Rolf A. Stahel +22 more
TL;DR: This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy and it is concluded that in biologically unselected patients, although associated with an improved ORR, pembrosumab improves neither PFS nor OS over single-agent chemotherapy.
References
More filters
Journal ArticleDOI
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Martin Reck,Delvys Rodriguez-Abreu,Andrew G. Robinson,Rina Hui,Tibor Csőszi,Andrea Fülöp,Maya Gottfried,Nir Peled,Ali Tafreshi,Sinead Cuffe,Mary O'Brien,Suman Rao,Katsuyuki Hotta,Melanie A. Leiby,Gregory M. Lubiniecki,Yue Shentu,Reshma A. Rangwala,Julie R. Brahmer +17 more
TL;DR: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express PD-L1 as mentioned in this paper.
Journal ArticleDOI
Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer
Scott J. Antonia,A. Villegas,Davey B. Daniel,David Vicente,Shuji Murakami,Rina Hui,Takashi Yokoi,Alberto Chiappori,Ki Hyeong Lee,Maike de Wit,Byoung Chul Cho,M. Bourhaba,Xavier Quantin,Takaaki Tokito,Tarek Mekhail,David Planchard,Young-Chul Kim,Christos S. Karapetis,Sandrine Hiret,Gyula Ostoros,Kaoru Kubota,Jhanelle E. Gray,Luis Paz-Ares,Javier de Castro Carpeño,Catherine Wadsworth,Giovanni Melillo,Haiyi Jiang,Y. Huang,Phillip A. Dennis,Mustafa Ozguroglu,Pacific Investigators +30 more
TL;DR: Progression‐free survival was significantly longer with durvalumab than with placebo, and safety was similar between the groups, and the secondary end points also favored durvalsumab.
Journal ArticleDOI
Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden
Matthew D. Hellmann,Tudor-Eliade Ciuleanu,Adam Pluzanski,Jong-Seok Lee,Gregory A. Otterson,Clarisse Audigier-Valette,Elisa Minenza,Helena Linardou,Sjaak Burgers,Pamela Salman,Hossein Borghaei,Suresh S. Ramalingam,Julie R. Brahmer,Martin Reck,Kenneth J. O'Byrne,William J. Geese,George Green,Han Chang,Joseph D. Szustakowski,Prabhu Bhagavatheeswaran,Diane Healey,Yali Fu,F. E. Nathan,Luis Paz-Ares +23 more
TL;DR: The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups, including patients with a PD‐L1 expression level of at least 1% and those with a level of less than 1%.
Journal ArticleDOI
IFN- γ –related mRNA profile predicts clinical response to PD-1 blockade
Mark Ayers,Jared Lunceford,Michael Nebozhyn,Erin Murphy,Andrey Loboda,David Ross Kaufman,Andrew Albright,Jonathan D. Cheng,S. Peter Kang,Veena Shankaran,Sarina Anne Piha-Paul,Jennifer H. Yearley,Tanguy Y. Seiwert,Antoni Ribas,Terrill K. McClanahan +14 more
TL;DR: The T cell–inflamed GEP contained IFN-&ggr;–responsive genes related to antigen presentation, chemokine expression, cytotoxic activity, and adaptive immune resistance, and these features were necessary, but not always sufficient, for clinical benefit.
Journal ArticleDOI
Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1.
Stéphane Champiat,Stéphane Champiat,Laurent Dercle,Samy Ammari,Christophe Massard,Antoine Hollebecque,Sophie Postel-Vinay,Sophie Postel-Vinay,Nathalie Chaput,Alexander M.M. Eggermont,Aurélien Marabelle,Aurélien Marabelle,Jean-Charles Soria,Jean-Charles Soria,Charles Ferté,Charles Ferté +15 more
TL;DR: A novel aggressive pattern of hyperprogressive disease or HPD exists in a fraction of patients treated with anti-PD-1/PD-L1 monotherapy, and this observation raises some concerns about treating elderly patients (>65 years old), and suggests further study of this phenomenon.
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