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Yang Yang, Jiaomiao Pei, Guozhen Gao, Zheng Yang, Shuzhong Guo, Bo Yue, Jianhua Qiu
We conducted a network meta-analysis in order to compare different strategies for managing melanoma patients. Electronic databases were searched for eligible randomized trials that compared different strategies in efficacy and tolerability. Five interventions were associated with a significant improvement in PFS over chemotherapy (all HR < 1): Ipilimumab, Tremelimumab, Nivolumab, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab. Three interventions exhibited significantly improved OS results over chemotherapy (all HR < 1): Ipilimumab, Nivolumab and Ipilimumab + Chemotherapy...
October 13, 2016: Oncotarget
G Santabarbara, P Maione, A Rossi, G Palazzolo, C Gridelli
INTRODUCTION: Lung cancers remain the principal cause of death cancer-related worldwide with a poor survival rate at five years from diagnosis. In patients with NSCLC harboring specific genetic alterations the anti EGFR TKIs and the ALK TKIs have improved the response rate and the quality of life compared to standard platinum-based chemotherapy. New approaches possibly applicable at the major of patients are needed. AREAS COVERED: The discovery that the immune system plays a fundamental role in the fight against cancer...
September 23, 2016: Expert Review of Clinical Pharmacology
Elia Moreno-Cubero, Juan-Ramón Larrubia
Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8(+) T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment...
July 28, 2016: World Journal of Gastroenterology: WJG
O Abdel-Rahman, D Helbling, J Schmidt, U Petrausch, A Giryes, A Mehrabi, O Schöb, M Mannhart, A Zidan, H Oweira
AIMS: Fatigue is one of the most prominent side-effects of immune checkpoint inhibition. Therefore, we assessed the risk of fatigue associated with inhibitors of the immune checkpoints. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, nivolumab, pembrolizumab and tremelimumab...
October 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
David Planchard, Takashi Yokoi, Michael J McCleod, Jürgen R Fischer, Young-Chul Kim, Marc Ballas, Kelvin Shi, Jean-Charles Soria
Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status...
May 2016: Clinical Lung Cancer
T Mok, P Schmid, O Arén, O Arrieta, M Gottfried, A R Jazieh, R Ramlau, K Timcheva, C Martin, S McIntosh
No abstract text is available yet for this article.
April 2016: Journal of Thoracic Oncology
S Peters, S Antonia, S B Goldberg, J V Heymach, E S Kim, K Nakagawa, V Papadimitrakopoulou, P Mukhopadhyay, S McIntosh, N A Rizvi
No abstract text is available yet for this article.
April 2016: Journal of Thoracic Oncology
Begoña Comin-Anduix, Helena Escuin-Ordinas, Francisco Javier Ibarrondo
The immune checkpoint therapy is a relatively recent strategy that aims to tweak the immune system to effectively attack cancer cells. The understanding of the immune responses and their regulation at the intracellular level and the development of fully humanized monoclonal antibodies are the pillars of an approach that could elicit durable clinical responses and even remission in some patients with cancer. Most of the immune checkpoints that regulate the T-cell responses (activation and inhibition) operate through proteins present on the cytoplasmic membrane of the immune cells...
2016: OncoTargets and Therapy
Tomohiro F Nishijima, Hyman B Muss, Shlomit S Shachar, Stergios J Moschos
BACKGROUND: Immune checkpoint inhibitors (ICIs) rely on the presence of ongoing immune response to exert their antitumor effect. Little is known whether an age-related decline in immune function negatively influences antitumor response and in so doing diminishes the efficacy of ICIs in elderly subjects. We performed a meta-analysis to compare the efficacy of ICIs between younger and older patients. PATIENTS AND METHODS: PubMed and the ASCO databases were searched up to September 2015...
April 2016: Cancer Treatment Reviews
Martin Reck, David Heigener, Niels Reinmuth
Treatment for small-cell lung cancer (SCLC) has changed little over the past few decades; available therapies have failed to extend survival in advanced disease. In recent years, immunotherapy with treatments such as interferons, TNFs, vaccines and immune checkpoint inhibitors has advanced and shown promise in the treatment of several tumor types. Immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab, durvalumab, tremelimumab and ulocuplumab are at the forefront of immunotherapy and have achieved approvals for certain cancer types, including melanoma (ipilimumab, nivolumab and pembrolizumab), non-SCLC (nivolumab and pembrolizumab) and renal cell carcinoma (nivolumab)...
April 2016: Future Oncology
Scott Antonia, Sarah B Goldberg, Ani Balmanoukian, Jamie E Chaft, Rachel E Sanborn, Ashok Gupta, Rajesh Narwal, Keith Steele, Yu Gu, Joyson J Karakunnel, Naiyer A Rizvi
BACKGROUND: PD-L1 and CTLA-4 immune checkpoints inhibit antitumour T-cell activity. Combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab might provide greater antitumour activity than either drug alone. We aimed to assess durvalumab plus tremelimumab in patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC). METHODS: We did a multicentre, non-randomised, open-label, phase 1b study at five cancer centres in the USA...
March 2016: Lancet Oncology
L Marthey, C Mateus, C Mussini, M Nachury, S Nancey, F Grange, C Zallot, L Peyrin-Biroulet, J F Rahier, M Bourdier de Beauregard, L Mortier, C Coutzac, E Soularue, E Lanoy, N Kapel, D Planchard, N Chaput, C Robert, F Carbonnel
BACKGROUND: Therapeutic monoclonal anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies are associated with immune-mediated enterocolitis. The aim of this study was to provide a detailed description of this entity. METHODS: We included patients with endoscopic signs of inflammation after anti-CTLA-4 infusions for cancer treatment. Other causes of enterocolitis were excluded. Clinical, biological and endoscopic data were recorded. A single pathologist reviewed endoscopic biopsies and colectomy specimens from 27 patients...
April 2016: Journal of Crohn's & Colitis
Janice M Reichert
The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016...
2016: MAbs
Alice Guazzelli, Michelle Hussain, Marija Krstic-Demonacos, Luciano Mutti
INTRODUCTION: Tremelimumab demonstrated therapeutic activity in different malignancies, including malignant pleural mesothelioma (MPM); however, continued research could improve the therapeutic index of this agent. AREAS COVERED: This review describes tremelimumab's clinical efficacy, administration and safety in patients affected with MPM and reports the state of the art clinical trials of tremelimumab. A literature search using the PubMed database was conducted using the search terms tremelimumab, MPM, current therapy, immune checkpoint blockage and cytotoxic T lymphocyte-associated antigen-4...
2015: Expert Opinion on Biological Therapy
Omar Abdel-Rahman, Hesham ElHalawani, Mona Fouad
AIM: We performed a meta-analysis of the risk of selected gastrointestinal toxicities associated with immune checkpoint inhibitors. PATIENTS & METHODS: Eligible studies included randomized trials of patients with solid tumors on ipilimumab, nivolumab, pembrolizumab, tremelimumab, pidilizumab and atezolizumab, describing events of diarrhea, vomiting or colitis. RESULTS: After exclusion of ineligible studies, a total of ten clinical trials were considered eligible for the meta-analysis...
2015: Immunotherapy
Joanna Mangana, Phil F Cheng, Katja Schindler, Benjamin Weide, Ulrike Held, Anna L Frauchiger, Emanuella Romano, Katharina C Kähler, Sima Rozati, Markus Rechsteiner, Holger Moch, Olivier Michielin, Claus Garbe, Axel Hauschild, Christoph Hoeller, Reinhard Dummer, Simone M Goldinger
Ipilimumab and tremelimumab are human monoclonal antibodies (Abs) against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival in advanced melanoma patients. Currently, there is no proven association between the BRAFV600 mutation and the disease control rate in response to ipilimumab. This analysis was carried out to assess if BRAFV600 and NRAS mutation status affects the clinical outcome of anti-CTLA-4-treated melanoma patients...
2015: PloS One
Zeynep Eroglu, Dae Won Kim, Xiaoyan Wang, Luis H Camacho, Bartosz Chmielowski, Elizabeth Seja, Arturo Villanueva, Kathleen Ruchalski, John A Glaspy, Kevin B Kim, Wen-Jen Hwu, Antoni Ribas
PURPOSE: One of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. Tremelimumab is an anti-CTLA-4 antibody of immunoglobulin G2 (IgG2) isotype initially tested in patients with advanced melanoma over 12 years ago. METHODS: We reviewed the outcomes of patients with advanced melanoma enrolled in four phase 1 and 2 tremelimumab trials at two sites to determine response rates and long-term survival...
November 2015: European Journal of Cancer
Anne Bertrand, Marie Kostine, Thomas Barnetche, Marie-Elise Truchetet, Thierry Schaeverbeke
BACKGROUND: Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic T-lymphocyte proliferation. This induction of a tolerance break against the tumor may be responsible for immune-related adverse events (irAEs). Our objective was to assess the incidence and nature of irAEs in oncologic patients receiving anti-CTLA-4 antibodies (ipilimumab and tremelimumab). METHODS: A systematic search of literature up to February 2014 was performed in MEDLINE, EMBASE, and Cochrane databases to identify relevant articles...
2015: BMC Medicine
Omar Abdel-Rahman, Hesham ElHalawani, Mona Fouad
BACKGROUND: We performed a meta-analysis of the risk of cutaneous toxicities associated with immune checkpoint inhibitors. METHODS: Eligible studies included randomized trials of patients with solid tumors on immune checkpoint inhibitors (ipilimumab, nivolumab, tremelimumab, pidlizumab and pembrolizumab); describing events of rash, vitiligo and pruritus. RESULTS: A total of nine clinical trials were considered eligible for the meta-analysis...
2015: Future Oncology
A Gupta, K M De Felice, E V Loftus, S Khanna
BACKGROUND: Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) has an important role in T-cell regulation, proliferation and tolerance. Anti-CTLA-4 agents, such as ipilimumab and tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune-related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common...
August 2015: Alimentary Pharmacology & Therapeutics
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