Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients
Guillermo de Velasco,Youjin Je,Dominick Bossé,Mark M. Awad,Patrick A. Ott,Raphael Brandao Moreira,Fabio A.B. Schutz,Joaquim Bellmunt,Guru Sonpavde,F. Stephen Hodi,Toni K. Choueiri +10 more
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TLDR
There is substantial evidence that ICIs are associated with a small but significant increase in risk of selected all-grade irAEs and high-grade gastrointestinal and liver toxicities, and AEs should be recognized promptly as early interventions may alleviate future complications.Citations
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Development of cancer immunotherapy based on PD-1/PD-L1 pathway blockade
Min Zhang,Kehai Liu,Mingfu Wang +2 more
TL;DR: A review of the main reasons that caused the low response rate of PD-/PD-L1 blockade therapy suggests the combination therapy based on PD-1/PD/L1 inhibitors and other therapeutics that can complement and promote each other to achieve improved immune response should be considered.
Journal ArticleDOI
The role of macrophages type 2 and T-regs in immune checkpoint inhibitor related adverse events.
Daniela Mihic-Probst,Michael Reinehr,Susanne Dettwiler,Isabel Kolm,Christian Britschgi,Ken Kudura,Ewerton Marques Maggio,Daniela Lenggenhager,Elisabeth J. Rushing +8 more
TL;DR: The study suggests that T cell activation is only partially responsible for irAE, and underlines the systemic involvement as well as the importance of monitoring cortisol levels to avoid potentially life threatening hypocortisolism.
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The pattern of time to onset and resolution of immune-related adverse events caused by immune checkpoint inhibitors in cancer: A pooled analysis of 23 clinical trials and 8,436 patients.
Si-Qi Tang,Cheng Xu,Ling-Long Tang,Yan Ping Mao,Wen-Fei Li,Lei Chen,Yuan Zhang,Ying Guo,Qing Liu,Ying Sun,Jun Ma +10 more
TL;DR: This data indicates that suppression of immune-related cell reprograming in mice treated with an ICI acts as a ‘spatially aggregating force’ to reprogram the immune system to attack cancer cells.
Journal ArticleDOI
Emerging Management Approach for the Adverse Events of Immunotherapy of Cancer
M. M. Rahman,Tapan Behl,Md. Rezaul Islam,Md. Noor Kutubul Alam,Mohaimenul Islam,Ali Albarrati,Mohammed Al-Bratty,Abdulkarim M. Meraya,Simona Bungau +8 more
TL;DR: A fundamental overview of immunotherapy and cancer-related side effect management strategies is given and the risk of life-threatening toxicities should not be underestimated.
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Immune-related adverse events following administration of anti-cytotoxic T-lymphocyte-associated protein-4 drugs: a comprehensive systematic review and meta-analysis.
TL;DR: Anti-CTLA-4 therapies are associated with an increased risk of serious organ-specific irAEs, most frequently involving the gastrointestinal system; however, no increasedrisk of hematologic abnormalities or severe musculoskeletal disorders was detected compared with other therapies.
References
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Bias in meta-analysis detected by a simple, graphical test
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Journal ArticleDOI
Meta-Analysis in Clinical Trials*
TL;DR: This paper examines eight published reviews each reporting results from several related trials in order to evaluate the efficacy of a certain treatment for a specified medical condition and suggests a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
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Operating characteristics of a rank correlation test for publication bias.
TL;DR: In this paper, an adjusted rank correlation test is proposed as a technique for identifying publication bias in a meta-analysis, and its operating characteristics are evaluated via simulations, and the test statistic is a direct statistical analogue of the popular funnel-graph.
Journal ArticleDOI
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Journal ArticleDOI
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
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