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SCLC “immune checkpoint inhibitors”

Yijun Jia, Xuefei Li, Tao Jiang, Sha Zhao, Chao Zhao, Limin Zhang, Xiaozhen Liu, Jinpeng Shi, Meng Qiao, Jiawei Luo, Sangtian Liu, Ruoshuang Han, Chunxia Su, Shengxiang Ren, Caicun Zhou
Immune checkpoint inhibitors targeting the programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway have profoundly improved the clinical management of non-small-cell lung cancer (NSCLC). Nevertheless, the superiority of single-agent PD-1/PD-L1 inhibitors in pretreated EGFR mutant patients has turned out to be moderate. One proposed mechanism for poor response to immune checkpoint inhibitors is an immunosuppressive tumor microenvironment. Therefore, we utilized two autochthonous EGFR-driven lung tumor models to investigate dynamic microenvironmental responses to EGFR-TKI treatment...
February 5, 2019: International Journal of Cancer. Journal International du Cancer
Lizza E L Hendriks, Clemence Henon, Edouard Auclin, Laura Mezquita, Roberto Ferrara, Clarisse Audigier-Valette, Julien Mazieres, Corentin Lefebvre, Audrey Rabeau, Sylvestre Le Moulec, Sophie Cousin, Boris Duchemann, Cecile le Pechoux, Angela Botticella, Samy Ammari, Anas Gazzah, Caroline Caramella, Julien Adam, Emmanuèle Lechapt, David Planchard, Dirk de Ruysscher, Anne-Marie Dingemans, Benjamin Besse
INTRODUCTION: although frequent in non-small cell lung cancer (NSCLC), brain metastases (BM) patients are often excluded from immune checkpoint inhibitor (ICI) trials. We evaluated BM outcome in a less selected NSCLC cohort. METHODS: data from consecutive advanced ICI treated NSCLC patients were collected. 'Active' BM: new and/or growing lesions without any subsequent local treatment before ICI start. Objective response rate (ORR), progression free survival (PFS) and overall survival (OS) were evaluated...
February 16, 2019: Journal of Thoracic Oncology
Kirstin Perdrizet, Natasha B Leighl
The treatment of advanced non-small cell lung cancer (NSCLC) has evolved to include targeted therapy, immunotherapy as well as chemotherapy for selected patients in the first-line setting. Angiogenesis inhibitors have been used in combination with chemotherapy in the first-line and maintenance settings providing improved progression-free survival (PFS) and objective response rate (ORR), as well as overall survival (OS) in selected studies. Biologic rationale exists for combining anti-angiogenic agents with immunotherapy and targeted kinase inhibitors (TKIs)...
February 18, 2019: Current Treatment Options in Oncology
Triparna Sen, B Leticia Rodriguez, Limo Chen, Carminia Della Corte, Naoto Morikawa, Junya Fujimoto, Sandra Cristea, Thuyen Nguyen, Lixia Diao, Lerong Li, Youhong Fan, Yongbin Yang, Jing Wang, Bonnie S Glisson, Ignacio I Wistuba, Julien Sage, John V Heymach, Don L Gibbons, Lauren Averett Byers
Despite recent advances in the use of immunotherapy, only a minority of small cell lung cancer (SCLC) patients respond to immune checkpoint blockade (ICB). Here, we show that targeting DNA damage response (DDR) proteins, poly ADP-ribose polymerase (PARP) and checkpoint kinase 1 (CHK1) significantly increased protein and surface expression of PD-L1. PARP or CHK1 inhibition remarkably potentiated the anti-tumor effect of PD-L1 blockade and augmented cytotoxic T-cell infiltration in multiple immunocompetent SCLC in vivo models...
February 18, 2019: Cancer Discovery
Panagiotis I Georgianos, Vasilios Vaios, Eleni Leontaridou, Georgia Karayannopoulou, Triantafyllia Koletsa, Athanasios Sioulis, Elias V Balaskas, Pantelis E Zebekakis
Immune-checkpoint-inhibitors (ICPIs) represent a novel class of immunotherapy against several malignancies. These agents are associated with several "immune-mediated" adverse effects, but the reported renal toxicity of ICPIs is less well defined. We present the case of a 60-year-old man with a history of non-small cell lung cancer, who developed acute kidney injury (AKI) approximately 3.5 months after initiation of immunotherapy with nivolumab. Urinalysis revealed sterile pyuria, without microscopic hematuria or proteinuria...
2019: Case Reports in Nephrology
Léa Berland, Simon Heeke, Olivier Humbert, Adam Macocco, Elodie Long-Mira, Sandra Lassalle, Virginie Lespinet-Fabre, Salomé Lalvée, Olivier Bordone, Charlotte Cohen, Sylvie Leroy, Véronique Hofman, Paul Hofman, Marius Ilié
In the last few years, the treatment of patients with non-small cell lung cancer (NSCLC) has impressively benefitted from immunotherapy, in particular from the inhibition of immune checkpoints such as programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1). However, despite the significant survival benefit for some patients with advanced NSCLC, the objective response rates (ORRs) remain relatively low no more than 20-30% with a large proportion of patients demonstrating primary resistance...
January 2019: Journal of Thoracic Disease
Hélène Blons, Simon Garinet, Pierre Laurent-Puig, Jean-Baptiste Oudart
Immunotherapy represents one of the most promising therapeutic approaches in lung cancer, however 50% of lung cancer patients will not respond to this treatment, while others will have transitory or durable responses. Because side effects may be life threatening and treatment costs remain very high, the identification of predictive markers is mandatory and actually extensively studied. Factors that determine response to immune checkpoint inhibitors (ICI) are numerous including tumor microenvironment, immune tumor infiltrates, expression of immune checkpoint proteins (PD-1/PD-L1), gene expression signatures and molecular tumor profiles...
January 2019: Journal of Thoracic Disease
Amanda Vannitamby, Shona Hendry, Tanvi Makadia, Janine Danks, John Slavin, Louis Irving, Daniel Steinfort, Steven Bozinovski
Multiple biomarkers are under evaluation to guide the use of immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC), including programed death ligand 1 (PD-L1) tumor cell staining. We have developed a new approach that accurately quantifies PD-L1 status and identifies multiple mutations by using a single bronchoscopy specimen. A novel molecular marker was identified to detect the presence of malignant cells in radial endobronchial ultrasound bronchial brushings from NSCLC (n = 15) and benign (n = 13) nodules by quantitative real-time RT-PCR (RT-qPCR)...
February 8, 2019: Journal of Molecular Diagnostics: JMD
Patrick Pilie, Carl M Gay, Lauren Averett Byers, Mark J O'Connor, Timothy A Yap
A mounting body of evidence now indicates that PARP inhibitors have the potential to be used as a foundation for both monotherapy and combination strategies across a wide spectrum of molecular backgrounds and tumor types. While PARP inhibitors as a class display many similarities, critical differences in structure can translate into differences in tolerability and antitumor activity that have important implications for the clinic. Furthermore, while PARP inhibitors have demonstrated a clear role in treating tumors with underlying homologous recombination deficiencies, there is now biological and early clinical evidence to support their use in other molecular subsets of cancer, including tumors associated with high levels of replication stress such as small cell lung cancer...
February 13, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
M Wiesweg, F Mairinger, H Reis, M Goetz, R F H Walter, T Hager, M Metzenmacher, W E E Eberhardt, A McCutcheon, J Köster, M Stuschke, C Aigner, K Darwiche, K W Schmid, S Rahmann, M Schuler
No abstract text is available yet for this article.
February 11, 2019: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Margaret Ottaviano, Sabino De Placido, Paolo Antonio Ascierto
AbstractSeveral researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient's immune system in the way of restore or induce a response to cancer. As a consequence, "cancer immunotherapy" is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of anti-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the treatment of a variety of malignancies...
February 12, 2019: Virchows Archiv: An International Journal of Pathology
Jingyi Chen, Yusong Chen, Fenglan Feng, Cheng Chen, Haikang Zeng, Shuai Wen, Xin Xu, Jianxing He, Jin Li
Background: Cytokine-induced killer (CIK) cells and natural killer (NK) cells are employed by two different approaches to adoptive cell immunotherapy for cancer. It has been reported that adoptive cell immunotherapy could prolong the overall survival (OS) of advanced cancer patients. The introduction of agents that induce immune checkpoint blockades has improved the efficacy of immune-mediated therapy for metastatic cancers. However, the effects of combining a checkpoint inhibitor with CIK cells or NK cells to target non-small cell lung cancer (NSCLC)remain unknown...
December 2018: Journal of Thoracic Disease
Kaikai Shen, Jinggang Cui, Yuqing Wei, Xiaojun Chen, Guohua Liu, Xiaolai Gao, Wei Li, Huiling Lu, Ping Zhan, Tangfeng Lv, Dang Lin
Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been applied as a first-line treatment for lung cancer, but consistent beneficial results have not been documented. Therefore, our meta-analysis aimed to evaluate the effectiveness and safety of combination therapy to promote its application. Methods: We searched electronic databases for studies that estimated the safety and efficacy of combined therapy. The objective response rate (ORR) and disease control response (DCR) parameters were evaluated with odds ratio (OR) values of the combination arm over the non-combination arm...
December 2018: Journal of Thoracic Disease
Courèche Kaderbhaï, Zoé Tharin, François Ghiringhelli
Immune checkpoint inhibitors radically changed the treatment of patients with non-small cell lung cancer (NSCLC). However, only one-quarter of patients benefit from these new therapies when used as monotherapy. The assessment of Program Death Ligand-1 (PD-L1) tumor expression by immunohistochemistry is used to select potential responder patients, but this not an optimal marker since it does not predict the absence of anti PD-1 efficacy. Despite this shortcoming, PD-L1 remains the gold standard biomarker in many studies and the only biomarker available for clinicians...
February 10, 2019: Cancers
Vaibhav Verma, Geeti Sharma, Abhijai Singh
Small cell lung cancer which constitutes about 15% of lung cancers is pathobiologically and clinically distinct from non small cell cancer. Histologically it is characterized by small cells with scant cytoplasm, absent or inconspicuous nucleoli, extensive necrosis, and expresses neuroendocrine markers. It is on a spectrum of neuroendocrine cancer that extend from typical carcinoids to large cell to small cell cancer. Clinically it behaves in a more malignant fashion with a rapid doubling time, early metastasis...
2019: Experimental Hematology & Oncology
Arnaud Jeanson, Pascale Tomasini, Maxime Souquet-Bressand, Nicolas Brandone, Mohamed Boucekine, Mathieu Grangeon, Solène Chaleat, Natalyia Khobta, Julie Milia, Laurent Mhanna, Laurent Greillier, Julie Biemar, Isabelle Nanni, L'houcine Ouafik, Stéphane Garcia, Julien Mazières, Fabrice Barlesi, Céline Mascaux
INTRODUCTION: KRAS mutation (KRASm) is the most frequent molecular alteration found in advanced non-small cell lung cancer (NSCLC), is associated with a poor prognosis, without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICI), and data about its efficacy in patients with KRASm NSCLC are discordant. This study assessed the routine efficacy of ICI in advanced KRASm NSCLC. METHODS: In this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICI and with available molecular analysis between April 2013 and June 2017...
February 6, 2019: Journal of Thoracic Oncology
Alexandros Papachristofilou, Madeleine M Hipp, Ute Klinkhardt, Martin Früh, Martin Sebastian, Christian Weiss, Miklos Pless, Richard Cathomas, Wolfgang Hilbe, Georg Pall, Thomas Wehler, Jürgen Alt, Helge Bischoff, Michael Geißler, Frank Griesinger, Karl-Josef Kallen, Mariola Fotin-Mleczek, Andreas Schröder, Birgit Scheel, Anke Muth, Tobias Seibel, Claudia Stosnach, Fatma Doener, Henoch S Hong, Sven D Koch, Ulrike Gnad-Vogt, Alfred Zippelius
BACKGROUND: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses. METHODS: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy...
February 8, 2019: Journal for Immunotherapy of Cancer
Rui Chen, Xiaoming Hou, Liping Yang, Da Zhao
BACKGROUND: Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, and most clinically curable patients are diagnosed with locally advanced disease. Although the efficacy of standard platinum-based chemotherapy doublets is relatively limited. The effect of immune checkpoint inhibitors (ICIs) remains controversial, and its role in the first-line treatment of advanced NSCLC is obscure. Thus, we carried out a systematic review and meta-analysis to compare the efficacy and safety of ICIs for advanced NSCLC...
February 7, 2019: Thoracic Cancer
Ernest Nadal, Bartomeu Massuti, Manuel Dómine, Rosario García-Campelo, Manuel Cobo, Enriqueta Felip
Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)-programmed cell death ligand-1 (PD-L1) axis have shown promising results in non-small cell lung cancer (NSCLC) patients, some of them with persistent responses to these agents that form a population of long-term survivors. Despite the variable definition of PD-L1 positivity in tumors, an association between expression and response has been reasonably consistent in advanced NSCLC. In addition, the clinical efficacy of ICIs seems to be related to the genomic landscape of the tumor in terms of mutational burden and clonal neoantigens...
February 6, 2019: Cancer Immunology, Immunotherapy: CII
Masahiro Yamasaki, Wakako Daido, Naomi Saito, Kunihiko Funaishi, Takenori Okada, Kazuma Kawamoto, Yu Matsumoto, Naoko Matsumoto, Masaya Taniwaki, Nobuyuki Ohashi, Noboru Hattori
Background: Nivolumab is an immune checkpoint inhibitor (ICI) that has shown efficacy for treating non-small cell lung cancer and has become a standard therapy for previously treated non-small cell lung cancer. Moreover, immune-related adverse events of ICI therapy are well-known. Malignant pericardial effusions occasionally arise in patients with lung cancer. There have been a few reports of pericardial effusion in non-small cell lung cancer after nivolumab administration. However, the cause of this condition is controversial; the possibilities include serositis as an immune-related adverse event or pseudo-progression...
2019: Frontiers in Oncology
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