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https://www.readbyqxmd.com/read/29785577/atezolizumab-a-review-in-previously-treated-advanced-non-small-cell-lung-cancer
#1
REVIEW
Hannah A Blair
Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials...
May 21, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29782924/emerging-biomarkers-for-immune-checkpoint-inhibition-in-lung-cancer
#2
REVIEW
George Cyriac, Leena Gandhi
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker...
May 18, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29779430/intratumoral-immune-cells-expressing-pd-1-pd-l1-and-their-prognostic-implications-in-cancer-a-meta-analysis
#3
Younghoon Kim, Xianyu Wen, Nam Yun Cho, Gyeong Hoon Kang
BACKGROUND: The prognostic value of immune cells expressing programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) in cancer are controversial, and the potential differential impact of using tissue microarrays and whole tissue sections to assess the positivity of immune cells has not been addressed. METHODS: The current study included 30 eligible studies with 7251 patients that evaluated the relationship between tumor-infiltrating lymphocytes expressing PD-1/PD-L1 and overall survival and disease-free survival, or progression-free survival...
May 1, 2018: International Journal of Biological Markers
https://www.readbyqxmd.com/read/29777823/updated-efficacy-analysis-including-secondary-population-results-for-oak-a-randomized-phase-iii-study-of-atezolizumab-vs-docetaxel-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer
#4
L Fehrenbacher, J von Pawel, K Park, A Rittmeyer, D R Gandara, S Ponce Aix, J-Y Han, S M Gadgeel, T Hida, D L Cortinovis, M Cobo, D M Kowalski, F De Marinis, M Gandhi, B Danner, C Matheny, M Kowanetz, P He, F Felizzi, H Patel, A Sandler, M Ballinger, F Barlesi
INTRODUCTION: The efficacy and safety of atezolizumab vs docetaxel as second- or third-line treatment in patients with advanced non-small cell lung cancer in the primary (n=850; ITT850) and secondary (n=1225; ITT1225) efficacy populations of the randomized phase III OAK study at an updated data cutoff were assessed. METHODS: Patients received atezolizumab 1200mg or docetaxel 75mg/m2 intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively...
May 16, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29776963/combined-vegf-and-pd-l1-blockade-displays-synergistic-treatment-effects-in-an-autochthonous-mouse-model-of-small-cell-lung-cancer
#5
Lydia Meder, Philipp Schuldt, Martin Thelen, Anna Schmitt, Felix Dietlein, Sebastian Klein, Sven Borchmann, Kerstin Wennhold, Ignacija Vlasic, Sebastian Oberbeck, Richard Riedel, Alexandra Florin, Kristina Golfmann, Hans Anton Schlößer, Margarete Odenthal, Reinhard Büttner, Juergen Wolf, Michael Hallek, Marco Herling, Michael von Bergwelt-Baildon, Hans Christian Reinhardt, Roland T Ullrich
Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1 targeted therapy synergistically improves treatment outcome compared to anti-PD-L1 and anti-VEGF monotherapy. Mice treated with anti-PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double positive exhausted T cell phenotype...
May 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29775808/phase-ii-study-of-maintenance-pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-sclc
#6
Shirish M Gadgeel, Nathan A Pennell, Mary Jo Fidler, Balazs Halmos, Philip Bonomi, James Stevenson, Bryan Schneider, Ammar Sukari, Jaclyn Ventimiglia, Wei Chen, Cathy Galasso, Antoinette Wozniak, Julie Boerner, Gregory P Kalemkerian
PURPOSE: To assess the efficacy of maintenance pembrolizumab in extensive-stage small cell lung cancer (SCLC) patients, after treatment with platinum/etoposide. PATIENTS AND METHODS: Extensive-stage SCLC patients with a response or stable disease following induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg IV every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary endpoint of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary endpoint...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775807/fir-efficacy-safety-and-biomarker-analysis-of-a-phase-ii-open-label-study-of-atezolizumab-in-pd-l1-selected-patients-with-non-small-cell-lung-cancer
#7
David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases)...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#8
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29767245/mir-142-5p-regulates-cd4-t-cells-in-human-non-small-cell-lung-cancer-through-pd-l1-expression-via-the-pten-pathway
#9
Jun Wan, Xiean Ling, Bin Peng, Guanggui Ding
The present study aimed to evaluate the function of microRNA (miR)-142-5p on cancer immunity to induce apoptosis in human non-small cell lung cancer (NSCLC) and its mechanism. miR-142-5p expression was upregulated, and CD4+ T cell levels were reduced in patients with NSCLC. Overexpression of miR-142-5p expression inhibited the cancer effects of CD4+ T cells on NSCLC cell lines, and downregulation of miR-142-5p increased the cancer effects of CD4+ T cells on NSCLC cell lines, compared with the control group...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29764856/-tp53-stk11-and-egfr-mutations-predict-tumor-immune-profile-and-the-response-to-anti-pd-1-in-lung-adenocarcinoma
#10
Jerome Biton, Audrey Mansuet-Lupo, Nicolas Pécuchet, Marco Alifano, Hanane Ouakrim, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Francois Goldwasser, Karen Leroy, Jeremy Goc, Marie Wislez, Claire Germain, Pierre Laurent-Puig, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Hélène F Blons, Diane Damotte
PURPOSE: By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. EXPERIMENTAL DESIGN: We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29764752/successful-treatment-by-pembrolizumab-in-a-patient-with-end-stage-renal-disease-with-advanced-non-small-cell-lung-cancer-and-high-pd-l1-expression
#11
Shiho Ishizuka, Shinya Sakata, Chieko Yoshida, Akira Takaki, Sho Saeki, Kazuyoshi Nakamura, Kazuhiko Fujii
We report a 66-year-old Japanese male with end-stage renal disease (ESRD) and advanced non-small cell lung cancer (NSCLC) who was on hemodialysis. The patient harbored high programmed death ligand 1 (PD-L1) expression and was successfully treated with pembrolizumab. Laboratory examination upon diagnosis showed elevated serum creatinine (6.58 mg/dL). We administered pembrolizumab (200 mg/body) and repeated every 3 weeks. His renal dysfunction gradually progressed, hemodialysis was initiated after eight courses of pembrolizumab, and the antitumor effect was maintained at five months after hemodialysis initiation...
May 10, 2018: Respiratory Investigation
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#12
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
May 14, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29760834/a-case-series-of-two-patients-presenting-with-pericardial-effusion-as-first-manifestation-of-non-small-cell-lung-cancer-with-braf-mutation-and-expression-of-pd-l1
#13
Muhammad Mufti, Steven Ching, Sassan Farjami, Sharareh Shahangian, Serap Sobnosky
Lung cancer is the number one cause of cancer-related deaths in the United States. Involvement of pericardium occurs once cancer has progressed to stage IV which can cause massive effusion in the pericardial sac. This can lead to cardiac tamponade which can be fatal very quickly if untreated. The following is a two patient case series in which both patients presented with large pericardial effusion. The first patient sought medical attention due to new onset palpitations and was found to have hemorrhagic pericardial effusion and pulmonary embolism (PE)...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29760833/synchronous-presence-of-egfr-alk-driver-mutations-along-with-pd-l1-overexpression-in-a-resected-early-stage-non-small-cell-lung-cancer-a-case-report-and-review-of-literature
#14
Nishitha Thumallapally, Sara Parylo, Adarsh Vennepureddy, Uroosa Ibrahim, Alisa Sokoloff
Treatment of lung cancer has been revolutionized with development of drugs that target key driver mutations and immune checkpoints. Until recently, it was believed that these driver mutations are mutually exclusive. However, few reports have emerged citing the presence of both mutations either synchronously or metachronously. We describe a case report of lung adenocarcinoma harboring two driver mutations in the same tumor cells as well as exhibiting high PDL1 expression. We further discuss the possible association of these driver mutations with PDL1 expression...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29758930/the-potential-predictive-value-of-circulating-immune-cell-ratio-and-tumor-marker-in-atezolizumab-treated-advanced-non-small-cell-lung-cancer-patients
#15
Minglei Zhuo, Hanxiao Chen, Tianzhuo Zhang, Xue Yang, Jia Zhong, Yuyan Wang, Tongtong An, Meina Wu, Ziping Wang, Jing Huang, Jun Zhao
BACKGROUND: The PD-L1 antibody atezolizumab has shown promising efficacy in patients with advanced non-small cell lung cancer. But the predictive marker of clinical benefit has not been identified. OBJECTIVE: This study aimed to search for potential predictive factors in circulating blood of patients receiving atezolizumab. METHODS: Ten patients diagnosed with advanced non-small cell lung cancer were enrolled in this open-label observing study...
May 4, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29756991/the-immune-landscape-of-non-small-cell-lung-cancer-utility-of-cytologic-and-histologic-samples-obtained-through-minimally-invasive-pulmonary-procedures
#16
Jason Beattie, Lonny Yarmus, Momen Wahidi, M Patricia Rivera, Christopher Gilbert, Fabien Maldonado, Kasia Czarnecka, Angela Argento, Alexander Chen, Felix Herth, Daniel H Sterman
The success of immune checkpoint inhibitors and the discovery of useful biomarkers to predict response to these agents has shifted much of the focus of personalized care for advanced non-small cell lung cancer towards harnessing the immune response. With further advancement, more effective immunotherapy options will emerge along with more useful biomarkers. For patients with advanced disease, minimally invasive techniques will remain most appropriate for acquisition of tissue. This is in contrast to default gold-standard large tissue specimens obtained through surgical resection...
May 14, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29750425/increased-infiltration-of-macrophages-to-radioresistant-lung-cancer-cells-contributes-to-the-development-of-the-additional-resistance-of-tumor-cells-to-the-cytotoxic-effects-of-nk-cells
#17
Mingjing Shen, Yongbing Chen, Lijun Xu, Rongying Zhu, Xiang Xue, Ying Tsai, Peter C Keng, Soo Ok Lee, Yuhchyau Chen
In this study, in order to investigate the effects of increased macrophage infiltration to radioresistant lung tumors in regulating natural killer (NK) cell-mediated immunity, we examined whether the treatment of radioresistant cells with conditioned medium (CM) from phorbol myristate acetate (PMA)/interleukin (IL)-4 treated THP-1 cells (used as a tumor-associated macrophage source) leads to the development of the additional resistance of tumor cells to NK cell cytotoxicity. We found that the susceptibility of THP-1 CM-treated radioresistant cells to NK cell cytotoxicity was decreased compared to the non-treated cells...
May 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29748004/pd-l1-expression-in-circulating-tumor-cells-of-advanced-non-small-cell-lung-cancer-patients-treated-with-nivolumab
#18
Nicolas Guibert, Myriam Delaunay, Amélie Lusque, Nadia Boubekeur, Isabelle Rouquette, Estelle Clermont, Jean Mourlanette, Sandrine Gouin, Inge Dormoy, Gilles Favre, Julien Mazieres, Anne Pradines
BACKGROUND: Inhibitors of the PD-1/PD-L1 immune checkpoint have become a standard of care in non-small cell lung cancer (NSCLC). Patient selection, currently based on PD-L1 expression on tumor tissue, is limited by its temporal and spatial heterogeneity. We hypothesized that liquid biopsy with PD-L1 analysis on circulating tumor cells (CTCs) might overcome this limitation. METHODS: Blood samples were prospectively collected from patients with advanced NSCLC before nivolumab treatment and at the time of progression...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29746230/safety-of-programmed-death-1-pathway-inhibitors-among-patients-with-non-small-cell-lung-cancer-and-preexisting-autoimmune-disorders
#19
Giulia C Leonardi, Justin F Gainor, Mehmet Altan, Sasha Kravets, Suzanne E Dahlberg, Lydia Gedmintas, Roxana Azimi, Hira Rizvi, Jonathan W Riess, Matthew D Hellmann, Mark M Awad
Purpose Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non-small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown. Methods As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor...
May 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29742733/immunotherapy-for-pulmonary-squamous-cell-carcinoma-and-colon-carcinoma-with-pembrolizumab-a-case-report
#20
Yoshihiro Nozawa, Yuka Oka, Jun Oosugi, Shinichi Takemura
RATIONALE: Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of colorectal cancer patients. To our knowledge, this is the first report to show both the successful treatment of pulmonary squamous cell carcinoma (SCC) with pembrolizumab alongside histological and immunohistochemical findings of resected colon cancer under immunotherapy for lung cancer. PATIENT CONCERNS: This patient was a 70-year-old man who presented with a right lung tumor and simultaneous adenocarcinoma of the sigmoid colon...
May 2018: Medicine (Baltimore)
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