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pd-l1 and EGFR

Takaki Akamine, Kazuki Takada, Gouji Toyokawa, Fumihiko Kinoshita, Taichi Matsubara, Yuka Kozuma, Naoki Haratake, Shinkichi Takamori, Fumihiko Hirai, Tetsuzo Tagawa, Tatsuro Okamoto, Yasuto Yoneshima, Isamu Okamoto, Mototsugu Shimokawa, Yoshinao Oda, Yoichi Nakanishi, Yoshihiko Maehara
OBJECTIVES: Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients...
March 2018: Surgical Oncology
Marina Chiara Garassino, Byoung-Chul Cho, Joo-Hang Kim, Julien Mazières, Johan Vansteenkiste, Hervé Lena, Jesus Corral Jaime, Jhanelle E Gray, John Powderly, Christos Chouaid, Paolo Bidoli, Paul Wheatley-Price, Keunchil Park, Ross A Soo, Yifan Huang, Catherine Wadsworth, Phillip A Dennis, Naiyer A Rizvi
BACKGROUND: Immune checkpoint inhibitors are a new standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without EGFR tyrosine kinase or anaplastic lymphoma kinase (ALK) genetic aberrations (EGFR-/ALK-), but clinical benefit in patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) has not been shown. We assessed the effect of durvalumab (anti-PD-L1) treatment in three cohorts of patients with NSCLC defined by EGFR/ALK status and tumour expression of PD-L1...
March 12, 2018: Lancet Oncology
Yuta Takashima, Jun Sakakibara-Konishi, Yutaka Hatanaka, Kanako C Hatanaka, Yoshihito Ohhara, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoshihiro Matsuno, Masaharu Nishimura
BACKGROUND: Approximately 20% to 30% of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC...
February 19, 2018: Clinical Lung Cancer
Kentaro Inamura
Immunohistochemistry is a widely available technique that is less challenging and can provide clinically meaningful results quickly and cost-efficiently in comparison with other techniques. In addition, immunohistochemistry allows for the evaluation of cellular localization of proteins in the context of tumor structure. In an era of precision medicine, pathologists are required to classify lung cancer into specific subtypes and assess biomarkers relevant to molecular-targeted therapies. This review summarizes the hot topics of immunohistochemistry in lung cancer, including (i) adenocarcinoma vs squamous cell carcinoma; (ii) neuroendocrine markers; (iii) ALK, ROS1, and EGFR; (iv) PD-L1 (CD274); (v) lung carcinoma vs malignant mesothelioma; and (vi) NUT carcinoma...
March 14, 2018: Cancers
Véronique Hofman, Sandra Lassalle, Coraline Bence, Elodie Long-Mira, Sacha Nahon-Estève, Simon Heeke, Virginie Lespinet-Fabre, Catherine Butori, Marius Ilié, Paul Hofman
The identification of certain genomic alterations ( EGFR , ALK , ROS1 , BRAF ) or immunological markers (PD-L1) in tissues or cells has led to targeted treatment for patients presenting with late stage or metastatic lung cancer. These biomarkers can be detected by immunohistochemistry (IHC) and/or by molecular biology (MB) techniques. These approaches are often complementary but depending on, the quantity and quality of the biological material, the urgency to get the results, the access to technological platforms, the financial resources and the expertise of the team, the choice of the approach can be questioned...
March 13, 2018: Cancers
Fausto Petrelli, Mariangela Maltese, Gianluca Tomasello, Barbara Conti, Karen Borgonovo, Mary Cabiddu, Mara Ghilardi, Michele Ghidini, Rodolfo Passalacqua, Sandro Barni, Matteo Brighenti
Clinicopathologic and molecular characteristics of non-small-cell lung cancers (NSCLCs) associated with a strong expression of programmed death ligand 1 (PD-L1+ in > 5% of cells) have not been well elucidated. Expression of PD-L1 is a poor prognostic factor, but NSCLCs with higher levels of PD-L1 have greater benefit when treated with immunotherapy. We have performed a systematic review to synthesize the available evidence regarding clinicopathologic and molecular variables associated with PD-L1 expression in NSCLC...
February 21, 2018: Clinical Lung Cancer
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
Bo Lan, Chengxi Ma, Chengyan Zhang, Shoujie Chai, Pingli Wang, Liren Ding, Kai Wang
Objective: To assess the association between PD-L1 expression and driver gene mutations in patients with non-small-cell lung cancer (NSCLC). Method: We performed a meta-analysis of 26 studies (7541 patients) which were published from 2015 to 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated to describe the correlation. Subgroup analysis was performed based on population characteristics, types of PD-L1 antibodies and quality of individual studies...
January 26, 2018: Oncotarget
Qi Jiang, Mixue Xie, Mengye He, Feifei Yan, Xiaochen Zhang, Sufen Yu
Anti-PD-1/PD-L1 antibodies have been proved one of the most promising treatments against non-small cell lung cancer (NSCLC); however, whether anti-PD-1/PD-L1 antibodies can provide added benefits for pretreated patients with advanced NSCLC and which patients are most likely to benefit from anti-PD-1/PD-L1 therapy remain controversial. This meta-analysis evaluated the efficacy and safety between anti-PD-1/PD-L1 antibodies and docetaxel in previously treated, advanced NSCLC. PubMed, EMBASE and Cochrane library databases were systematically searched for eligible studies...
January 26, 2018: Oncotarget
Siddharth Sheth, Jared Weiss
Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2...
February 21, 2018: Future Oncology
Jae Kyeom Sim, Sang Mi Chung, Jong Hyun Choi, Jee Youn Oh, Seung Heon Lee, Je Hyeong Kim, Kyung Hoon Min, Gyu Young Hur, Jae Jeong Shim, Kyung Ho Kang, Bong Kyung Shin, Ju Han Lee, Sung Yong Lee
Background/Aims: Pulmonary sarcomatoid carcinoma (PSC) is a poorly differentiated non-small cell lung cancer (NSCLC) that contains components of spindle or giant cells. Owing to its low prevalence, there are insufficient data regarding its clinical features, therapeutic strategies and prognosis. Methods: The medical records of 26 patients diagnosed with PSC from January 2009 to June 2015 were reviewed and analyzed for clinicopathological characteristics, treatment modality, and outcomes...
February 20, 2018: Korean Journal of Internal Medicine
Steven B Maron, Lindsay Alpert, Heewon A Kwak, Samantha Lomnicki, Leah Chase, David Xu, Emily O'Day, Rebecca J Nagy, Richard B Lanman, Fabiola Cecchi, Todd Hembrough, Alexa Schrock, John Hart, Shu-Yuan Xiao, Namrata Setia, Daniel V T Catenacci
Previous anti-EGFR trials in unselected gastroesophageal adenocarcinoma (GEA) patients were resoundingly negative. We identified EGFR amplification in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven pts received >1 dose of treatment: three first line FOLFOX plus ABT-806, one second line FOLFIRI plus cetuximab, and three third/fourth line cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease control in 100% (7/7) with a median progression-free survival of 10 months...
February 15, 2018: Cancer Discovery
Conor E Steuer, Christopher C Griffith, Sreenivas Nannapaneni, Mihir R Patel, Yuan Liu, Kelly R Magliocca, Mark W El-Deiry, Cynthia Cohen, Taofeek K Owonikoko, Dong M Shin, Zhuo Georgia Chen, Nabil F Saba
We explored potential associations of the PD-1/PD-L1/PD-L2 pathway with clinical characteristics, outcome, and expression of EGFR, HER2, HER3 in oropharyngeal squamous cell carcinoma (OPSCC) using an institutional database. Protein expression was assessed by immunohistochemistry on tissue microarray sections (EGFR, HER2, HER3) or whole tissue sections (PD-1/PD-L1/PD-L2). Expression of EGFR, HER2, HER3, PD-L1, and PD-L2 was quantified on tumor cells. Maximum density of PD-1 positive lymphocytes was measured on a scale of 0-4 within the tumor mass and peritumoral stroma...
February 13, 2018: Molecular Cancer Therapeutics
Jai-Nien Tung, Po-Lin Lin, Yao-Chen Wang, De-Wei Wu, Chi-Yi Chen, Huei Lee
Programmed death ligand (PD-L1) expression was associated with tumor immune escape and subsequent poor prognosis in non-small cell lung cancer (NSCLC). This expression was higher in patients with EGFR-mutated NSCLC tumors than in those with EGFR-wild-type (WT) NSCLC tumors. We therefore hypothesized that poor prognosis mediated by higher PD-L1 may be partially through conferring resistance to tyrosine kinase inhibitor (TKI) in NSCLC regardless of EGFR mutation. The change in PD-L1 expression following gene manipulation corresponded with changes in expression of HIF-1α and YAP1...
January 12, 2018: Oncotarget
Paul A VanderLaan, Deepa Rangachari, Adnan Majid, Mihir S Parikh, Sidharta P Gangadharan, Michael S Kent, Danielle C McDonald, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice. METHODS: We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Kazuki Takada, Gouji Toyokawa, Tetsuzo Tagawa, Kenichi Kohashi, Mototsugu Shimokawa, Takaki Akamine, Shinkichi Takamori, Fumihiko Hirai, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara
OBJECTIVES: It was reported that programmed cell death-ligand 1 (PD-L1) expression is associated with smoking and wild-type epidermal growth factor receptor (EGFR) in lung adenocarcinoma. However, the association between PD-L1 expression and EGFR mutation site in EGFR mutation-positive lung adenocarcinoma is unclear. MATERIALS AND METHODS: We retrospectively examined the relationship between PD-L1 expression and EGFR status in 441 surgically resected primary lung adenocarcinomas...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Xing Song, Yingjie Shao, Tianwei Jiang, Yun Ding, Bin Xu, Xiao Zheng, Qi Wang, Xin Chen, Wendong Gu, Changping Wu, Jingting Jiang
BACKGROUND: In the present study, we aimed to investigate the role of epidermal growth factor receptor (EGFR) pathway in the up-regulation of programmed death ligand-1 (PD-L1) caused by radiotherapy (RT). MATERIALS AND METHODS: Tissue microarrays (TMA) consisting of glioma cancer specimens from 64 patients were used to examine the correlation between PD-L1 and EGFR levels. Furthermore, we performed in vitro experiments to assess the role of EGFR pathway in RT-upregulated PD-L1 expression using human glioma cell lines U87 and U251...
January 30, 2018: EBioMedicine
Irene Moya-Horno, Santiago Viteri, Niki Karachaliou, Rafael Rosell
Treatment for advanced non-small cell lung cancer (NSCLC) has been significantly improved in recent years with the incorporation of drugs targeting antiangiogenesis and more specifically genomic alterations such as the EGFR mutations and ALK translocations. However, most patients invariably progress and die. The emergence of immune checkpoint inhibitors targeting the pathways involved in tumor-induced immunosuppression have redefined the management of the disease, achieving significant long-lasting responses with manageable safety profiles, regardless of histology...
2018: Therapeutic Advances in Medical Oncology
Kenichi Kobayashi, Masahiro Seike, Fenfei Zou, Rintaro Noro, Mika Chiba, Arimi Ishikawa, Shinobu Kunugi, Kaoru Kubota, Akihiko Gemma
BACKGROUND/AIM: Recent clinical trials have shown that immune checkpoint blockades that target either PD-1 or PD-L1 yield remarkable responses in a subgroup of patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively examined, by immunohistochemical analysis, 211 NSCLC samples. Using 32 independent samples, we also evaluated PD-L1 expression in NSCLC patients with EGFR gene mutations treated by EGFR-TKIs. RESULTS: Overall survival of PD-L1-positive stages I-III NSCLC and stage I NSCLC and stages I-III squamous cell carcinoma (SQ) were significantly shorter than those of PD-L1-negative NSCLC (p<0...
February 2018: Anticancer Research
Akito Hata, Nobuyuki Katakami, Shigeki Nanjo, Chiyuki Okuda, Reiko Kaji, Katsuhiro Masago, Shiro Fujita, Hiroshi Yoshida, Kota Zama, Yukihiro Imai, Yukio Hirata
Background: Current clinical trials have suggested poorer efficacies of anti-programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) immunotherapies for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, implying lower PD-L1 expression in EGFR-mutant NSCLC than in EGFR-wild type. Methods: We retrospectively analyzed correlation between PD-L1 expression and EGFR status in clinical samples of pretreated NSCLC. PD-L1 immunohistochemistry was performed using the 28-8 anti-PD-L1 antibody for tumor cell membrane staining...
December 26, 2017: Oncotarget
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