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https://www.readbyqxmd.com/read/28529902/current-state-of-immunotherapy-for-non-small-cell-lung-cancer
#1
REVIEW
Jyoti Malhotra, Salma K Jabbour, Joseph Aisner
Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28515244/what-when-and-how-of-biomarker-testing-in-non-small-cell-lung-cancer
#2
Gregory L Riely
Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28507793/composite-biomarkers-defined-by-multiparametric-immunofluorescence-analysis-identify-alk-positive-adenocarcinoma-as-a-potential-target-for-immunotherapy
#3
Hélène Roussel, Eléonore De Guillebon, Lucie Biard, Marion Mandavit, Laure Gibault, Elisabeth Fabre, Martine Antoine, Paul Hofman, Michèle Beau-Faller, Hélène Blons, Claire Danel, Françoise Le Pimpec Barthes, Alain Gey, Clémence Granier, Marie Wislez, Pierre Laurent-Puig, Stéphane Oudard, Patrick Bruneval, Cécile Badoual, Jacques Cadranel, Eric Tartour
Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. Some predictive biomarkers of clinical response to this therapy are starting to emerge, such as PD-L1 expression by tumor/stromal cells and infiltration by CD8(+) T cells expressing PD-1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28460468/pd-l1-expression-and-its-relationship-with-oncogenic-drivers-in-non-small-cell-lung-cancer-nsclc
#4
Liyan Jiang, Xinying Su, Tianwei Zhang, Xiaolu Yin, Meizhuo Zhang, Haihua Fu, Hulin Han, Yun Sun, Lili Dong, Jialin Qian, Yanhua Xu, Xuan Fu, Paul R Gavine, Yanbin Zhou, Kun Tian, Jiaqi Huang, Dong Shen, Haiyi Jiang, Yihong Yao, Baohui Han, Yi Gu
In order to explore the potential patient population who could benefit from anti PD-1/PD-L1 mono or combination therapies, this study aimed to profile a panel of immunotherapy related biomarkers (PD-1, PD-L1, CTLA-4 and CD8) and targeted therapy biomarkers (EGFR, KRAS, ALK, ROS1 and MET) in NSCLC.Tumor samples from 297 NSCLC patients, including 156 adenocarcinomas (AD) and 129 squamous cell carcinomas (SCC), were analyzed using immunohistochemistry, immunofluorescence, sequencing and fluorescence in situ hybridization...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28435290/altered-status-of-programmed-death-ligand-1-after-recurrence-in-resected-lung-adenocarcinoma-patients
#5
Jun Chen, Hui Li, Ronglin Pang, Jia Huang
PURPOSE: Programmed death-ligand 1 (PD-L1) is found to be overexpressed in non-small cell lung cancer. The present study intended to evaluate the status of PD-L1 expression in patients with resection and recurrent lung adenocarcinoma. PATIENTS AND METHODS: Matched resection and recurrent tumor samples were harvested from 65 lung adenocarcinoma patients. Immunohistochemistry was used to evaluate the status of PD-L1 expression. Kaplan-Meier method was used for survival analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28423587/the-correlation-between-programmed-death-ligand-1-expression-and-driver-gene-mutations-in-nsclc
#6
Haitao Yang, Huijuan Chen, Shuimei Luo, Lina Li, Sijing Zhou, Ruifen Shen, Heng Lin, Xianhe Xie
OBJECTIVES: This study aimed to evaluate the correlation between positive PD-L1 expression and driver gene mutations in NSCLC and to seek preliminary evidence in favor of the strategy of PD-L1 inhibitors plus targeted agents. RESULTS: The overall analyses revealed that positive PD-L1 expression had a significant relationship with KRAS status (RR = 1.26; 95% CI, 1.06-1.50, P = 0.010), but no correlation with clinical characteristics (gender, smoking status, histological types), driver gene status (EGFR, ALK) and overall survival (OS): male versus female (RR = 1...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419182/molecular-classification-of-pulmonary-sarcomatoid-carcinomas-suggests-new-therapeutic-opportunities
#7
N Pécuchet, T Vieira, N Rabbe, M Antoine, H Blons, J Cadranel, P Laurent-Puig, M Wislez
Background: Pulmonary sarcomatoid carcinoma (SC) is a rare disease with poor prognosis and with strong inter- and intratumor heterogeneity. However, molecular classification is currently focused on activating MET mutations. We sought to better characterize the molecular diversity of SC using mutational signatures that reflect different mutational processes, such as tobacco-associated adducts (signature 4), BRCA1/BRCA2 deficiency (signature 3) or APOBEC enzyme deamination (signatures 2&13)...
April 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28416123/immune-checkpoint-inhibitors-for-patients-with-advanced-non-small-cell-lung-cancer-a%C3%A2-systematic-review
#8
REVIEW
Peter M Ellis, Emily T Vella, Yee C Ung
Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC...
February 16, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28407039/tumor-immune-microenvironment-and-nivolumab-efficacy-in-egfr-mutation-positive-non-small-cell-lung-cancer-based-on-t790m-status-after-disease-progression-during-egfr-tki-treatment
#9
K Haratani, H Hayashi, T Tanaka, H Kaneda, Y Togashi, K Sakai, K Hayashi, S Tomida, Y Chiba, K Yonesaka, Y Nonagase, T Takahama, J Tanizaki, K Tanaka, T Yoshida, K Tanimura, M Takeda, H Yoshioka, T Ishida, T Mitsudomi, K Nishio, K Nakagawa
Background.: The efficacy of programmed death-1 (PD-1) blockade in epidermal growth factor receptor gene ( EGFR ) mutation-positive non-small cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR . Patients and Methods.: We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A)...
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28387300/pd-l1-expression-in-lung-adenosquamous-carcinomas-compared-with-the-more-common-variants-of-non-small-cell-lung-cancer
#10
Xiaohua Shi, Shafei Wu, Jian Sun, Yuanyuan Liu, Xuan Zeng, Zhiyong Liang
Lung adenosquamous cell carcinomas (ASCs) is a rare variant of NSCLC with a poorer prognosis and fewer treatment option than the more common variants. PD-L1 expression is reported to be the predictor of clinical response in trials of NSCLC. In our study, PD-L1 expression was evaluated via immunohistochemistry using a specific monoclonal antibody (SP263), and PD-L1 mRNA expression was evaluated via in situ hybridization. This study included 51 ASCs, 133 lung adenocarcinomas, and 83 lung squamous cell carcinomas (SCC)...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373005/avelumab-for-patients-with-previously-treated-metastatic-or-recurrent-non-small-cell-lung-cancer-javelin-solid-tumor-dose-expansion-cohort-of-a-multicentre-open-label-phase-1b-trial
#11
James L Gulley, Arun Rajan, David R Spigel, Nicholas Iannotti, Jason Chandler, Deborah J L Wong, Joseph Leach, W Jeff Edenfield, Ding Wang, Hans Juergen Grote, Anja von Heydebreck, Kevin Chin, Jean-Marie Cuillerot, Karen Kelly
BACKGROUND: Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). METHODS: In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA...
March 31, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28363335/drug-biomarker-co-development-in-oncology-20-years-and-counting
#12
Julianne D Twomey, Nina N Brahme, Baolin Zhang
Predictive biomarkers for oncology are necessary to accurately identify patients who will benefit from anticancer treatment. Recently approved oncology drugs target discrete molecular aberrations or pathways in tumor cells and consequently are active on a subset of patient population, yet clinical studies have shown that not all biomarker-positive patients respond. The advancement of predictive biomarkers needs to detect novel and evolving drug resistance mechanisms, not only to guide the selection of patient subsets for specific treatments, but to identify new therapeutic targets...
January 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/28351930/hyper-progressors-after-immunotherapy-analysis-of-genomic-alterations-associated-with-accelerated-growth-rate
#13
Shumei Kato, Aaron Michael Goodman, Vighnesh Walavalkar, Donald A Barkauskas, Andrew Sharabi, Razelle Kurzrock
PURPOSE: Checkpoint inhibitors demonstrate salutary anti-cancer effects including long-term remissions. PD-L1 expression/amplification, high mutational burden and mismatch repair-deficiency correlate with response. We have, however, observed a subset of patients who appear to be "hyper-progressors," with a greatly accelerated rate of tumor growth and clinical deterioration compared to pre-therapy, which was also recently reported by Institut Gustave Roussy. The current study investigated potential genomic markers associated with "hyper-progression" after immunotherapy...
March 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28341875/pd-l1-overexpression-is-partially-regulated-by-egfr-her2-signaling-and-associated-with-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#14
Riki Okita, Ai Maeda, Katsuhiko Shimizu, Yuji Nojima, Shinsuke Saisho, Masao Nakata
Immunocheckpoint inhibitors targeting the programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) axis have shown promising results in patients with non-small-cell lung cancer (NSCLC). Recent research has shown that epidermal growth factor receptor (EGFR) signaling affects PD-L1 expression in NSCLC cells; however, the mechanism regulating PD-L1 expression in tumor cells remains unclear. Using immunohistochemistry, we evaluated the impact of expression of PD-L1 and EGF family receptors EGFR and human epidermal growth factor receptor 2 (HER2) in tumor cells from 91 patients with pathological Stage IA-IIIA NSCLC...
March 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28321814/immunotherapy-in-nsclc-a-promising-and-revolutionary-weapon
#15
Christian Rolfo, Christian Caglevic, Mariacarmela Santarpia, Antonio Araujo, Elisa Giovannetti, Carolina Diaz Gallardo, Patrick Pauwels, Mauricio Mahave
Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. Targeted therapies for EGFR and ALK mutant patients have showed better results when compared with chemotherapy, nevertheless most of patients will fail and need to be treated with chemotherapy if they still have a good performance status...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28319808/identifying-regulatory-posttranslational-modifications-of-pd-l1-a-focus-on-monoubiquitinaton
#16
Henrick Horita, Andy Law, Soonjin Hong, Kim Middleton
A set of high-affinity, high-specificity posttranslational modification (PTM) enrichment tools was developed to generate an unbiased snapshot of four key PTM profiles (tyrosine phosphorylation, acetylation, ubiquitination, and SUMOylation 2/3) for the clinically important protein programmed cell death ligand 1 (PD-L1). The results showed that epidermal growth factor (EGF) treatment induced tyrosine phosphorylation, acetylation, and ubiquitination of PD-L1. Further characterization of EGF-induced PD-L1 ubiquitination revealed a significant increase in mono- and multiubiquitination of PD-L1 that occurred on glycosylated PD-L1...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28301925/retrospective-molecular-epidemiology-study-of-pd-l1-expression-in-patients-with-egfr-mutant-non-small-cell-lung-cancer
#17
Jong Ho Cho, Wei Zhou, Yoon-La Choi, Jong-Mu Sun, Hyejoo Choi, Tae-Eun Kim, Marisa Dolled-Filhart, Kenneth Emancipator, Mary Anne Rutkowski, Jhingook Kim
Purpose: Data are limited on PD-L1 expression in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free (RFS) and overall survival in 319 patients with EGFR-mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS)...
March 17, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28297818/-research-progress-of-pd-1-pd-l1-pathway-in-non-small-cell-lung-cancer-with-egfr
#18
A Y Zhong, Y She, M H Shi
No abstract text is available yet for this article.
March 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28260924/impact-of-gefitinib-in-early-stage-treatment-on-circulating-cytokines-and-lymphocytes-for-patients-with-advanced-non-small-cell-lung-cancer
#19
Jin Sheng, Wenfeng Fang, Xia Liu, Shan Xing, Jianhua Zhan, Yuxiang Ma, Yan Huang, Ningning Zhou, Hongyun Zhao, Li Zhang
OBJECTIVES: The impact of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) on the human immune system remains undefined. This study illustrates the immunomodulatory effect of gefitinib in patients with advanced non-small cell lung cancer (NSCLC) and its relevant prognostic significance. PATIENTS AND METHODS: Peripheral blood samples were collected from 54 patients at baseline and after 4 weeks of gefitinib treatment. Circulating lymphocyte populations and cytokine levels were measured...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28259530/association-between-pd-l1-expression-and-driven-gene-status-in-nsclc-a-meta-analysis
#20
D Li, X Zhu, H Wang, N Li
PURPOSE: We explored the potential clinical association between programmed death-ligand 1 (PD-L1) expression and driven gene status in non-small cell lung cancer (NSCLC). METHODS: We systemically searched through October 2015. Odd ratios (ORs) with 95% CIs were calculated to examine the association of PD-L1 expression with driven gene status. A random- or fixed-effects model was used. RESULTS: Nine studies were identified. KRAS-mutant tumors were more likely to be PD-L1 positive than KRAS-wild type tumors (51% vs 36%; OR 1...
February 21, 2017: European Journal of Surgical Oncology
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