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https://www.readbyqxmd.com/read/27932067/nivolumab-plus-ipilimumab-as-first-line-treatment-for-advanced-non-small-cell-lung-cancer-checkmate-012-results-of-an-open-label-phase-1-multicohort-study
#1
Matthew D Hellmann, Naiyer A Rizvi, Jonathan W Goldman, Scott N Gettinger, Hossein Borghaei, Julie R Brahmer, Neal E Ready, David E Gerber, Laura Q Chow, Rosalyn A Juergens, Frances A Shepherd, Scott A Laurie, William J Geese, Shruti Agrawal, Tina C Young, Xuemei Li, Scott J Antonia
BACKGROUND: Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC. METHODS: The open-label, phase 1, multicohort study (CheckMate 012) cohorts reported here were enrolled at eight US academic centres. Eligible patients were aged 18 years or older with histologically or cytologically confirmed recurrent stage IIIb or stage IV, chemotherapy-naive NSCLC...
December 2, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27931835/management-of-patients-with-recurrent-advanced-cervical-cancer-beyond-first-line-platinum-regimens-where-do-we-stand-a-literature-review
#2
REVIEW
Stergios Boussios, Esmeralda Seraj, George Zarkavelis, Dimitrios Petrakis, Aristomenes Kollas, Aikaterini Kafantari, Abraam Assi, Konstantina Tatsi, Nicholas Pavlidis, George Pentheroudakis
BACKGROUND: Cervical cancer is the fourth most common cancer affecting women worldwide. Despite advances in screening and human papillomavirus (HPV) vaccination, a significant number of women present with or develop advanced disease. Palliative platinum-based chemotherapy (CT) is the standard first-line treatment for metastatic/recurrent cervical cancer. The prognosis remains poor and effective second line options are urgently needed. METHODS: We searched the English-language medical literature as well as relevant guideline databases, published from January 1981 to December 2015 and identified publications related to cervical cancer and its therapies...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27930644/immunotherapy-for-the-treatment-of-breast-cancer-checkpoint-blockade-cancer-vaccines-and-future-directions-in-combination-immunotherapy
#3
Heather L McArthur, David B Page
Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1). Both of these approaches currently are being explored as potential strategies for the treatment of breast cancer. Recent studies suggest that immunotherapy is poised to change the therapeutic landscape for some breast cancers...
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27929437/the-traditional-chinese-medicine-dangguibuxue-tang-sensitizes-colorectal-cancer-cells-to-chemoradiotherapy
#4
Shun-Ting Chen, Tzung-Yan Lee, Tung-Hu Tsai, Yin-Cheng Lin, Chin-Ping Lin, Hui-Ru Shieh, Ming-Ling Hsu, Chih-Wen Chi, Ming-Cheng Lee, Hen-Hong Chang, Yu-Jen Chen
Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. We examined whether DangguiBuxue Tang (DBT), a traditional Chinese herbal extract, sensitizes colorectal cancer cells to anticancer treatments. The polysaccharide-depleted fraction of DBT (DBT-PD) contains greater amounts of astragaloside IV (312.626 µg/g) and ferulic acid (1.404 µg/g) than does the original formula...
December 6, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27926518/higher-programmed-cell-death-1-ligand-1-pd-l1-mrna-level-in-clear-cell-renal-cell-carcinomas-is-associated-with-a-favorable-outcome-due-to-the-active-immune-responses-in-tumor-tissues
#5
Xiang-Hui Ning, Yan-Qing Gong, Shi-Ming He, Teng Li, Jiang-Yi Wang, Shuang-He Peng, Jin-Chao Chen, Jia-Yuan Liu, Nie-Nie Qi, Ying-Lu Guo, Kan Gong
Renal cell carcinoma is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in renal cell carcinomas in predicting outcome of the patients is yet unclear. We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer, 259 kidney papillary cell carcinoma and 66 kidney chromophobe patients from The Cancer Genome Atlas (TCGA) database. In kidney clear cell cancer patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925177/t-cell-diversification-reflects-antigen-selection-in-the-blood-of-patients-on-immune-checkpoint-inhibition-and-may-be-exploited-as-liquid-biopsy-biomarker
#6
Nuray Akyüz, Anna Brandt, Alexander Stein, Simon Schliffke, Thorben Mährle, Julia Quidde, Eray Goekkurt, Sonja Loges, Thomas Haalck, Christopher Ford, Anne Marie Asemissen, Benjamin Thiele, Janina Radloff, Toni Thenhausen, Artus Krohn-Grimberghe, Carsten Bokemeyer, Mascha Binder
Cancer immunotherapy with antibodies targeting immune checkpoints, such as programmed cell death protein 1 (PD-1), shows encouraging results, but reliable biomarkers predicting response to this costly and potentially toxic treatment approach are still lacking. To explore an immune signature predictive for response, we performed liquid biopsy immunoprofiling in 18 cancer patients undergoing PD-1 inhibition before and shortly after initiation of treatment by multicolor flow cytometry and next-generation T- and B-cell immunosequencing (TCRß/IGH)...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27925176/pd-l1-expression-of-the-residual-tumor-serves-as-a-prognostic-marker-in-local-advanced-breast-cancer-after-neoadjuvant-chemotherapy
#7
Sheng Chen, Ruo-Xi Wang, Yin Liu, Wen-Tao Yang, Zhi-Ming Shao
This study sought to investigate the prevalence of programmed death ligand 1 (PD-L1) and its prognostic value in patients with residual tumors after neoadjuvant chemotherapy (NCT) for locally advanced breast cancer (LABC). A total of 309 patients considered as non-pathological complete responders (non-pCR) after NCT followed by mastectomy were selected. The expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) in residual breast cancer cells was assessed by immunohistochemistry in surgical specimens...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27923550/treatment-design-and-rationale-for-a-randomized-trial-of-cisplatin-and-etoposide-plus-thoracic-radiotherapy-followed-by-nivolumab-or-placebo-for-locally-advanced-non-small-cell-lung-cancer-rtog-3505
#8
David E Gerber, James J Urbanic, Corey Langer, Chen Hu, I-Fen Chang, Bo Lu, Benjamin Movsas, Robert Jeraj, Walter J Curran, Jeffrey D Bradley
Radiation Therapy Oncology Group (RTOG) 3505 is a randomized phase 3 study of concurrent chemoradiation followed by immune checkpoint inhibitor therapy or placebo in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with surgically unresectable stage 3 NSCLC will receive thoracic radiotherapy to 60 Gy with concurrent cisplatin 50 mg/m(2) intravenously (I.V.) on days 1, 8, 29, and 36, and etoposide 50 mg/m(2) I.V. on days 1 to 5 and days 29 to 33. Between 4 and 12 weeks after completion of concurrent chemoradiation, eligible patients will be randomized to the anti-programmed death 1 (PD-1) monoclonal antibody nivolumab 240 mg I...
October 26, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27920704/autoimmune-hemolytic-anemia-as-a-complication-of-nivolumab-therapy
#9
Amruth R Palla, Devin Kennedy, Hossain Mosharraf, Donald Doll
Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920143/targeting-immune-suppression-in-cancer
#10
(no author information available yet)
Researchers have figured out a way to switch the immunosuppressive phenotype of tumor-associated macrophages to one that's immunostimulatory. By inhibiting PI3Kγ in these macrophages, they significantly suppressed tumor growth in mice; when anti-PD-1 therapy was added to PI3Kγ inhibition, complete and sustained tumor eradication was observed in many cases.
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27914100/transient-immunological-and-clinical-effectiveness-of-treating-mice-bearing-premalignant-oral-lesions-with-pd-1-antibodies
#11
Corinne A Levingston, M Rita I Young
A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the impact of blocking PD-1 on cytokine expression and on progression of lesions to cancer. The results of this study show increased production of IL-2 and the inflammatory cytokines IL-6, IL-17 and TNF-α by spleen cells of lesion-bearing mice that were treated with PD-1 antibody for one week compared to cytokine production by spleen cells of lesion-bearing mice treated with control antibody. Production of IFN-γ increased at 3 weeks of PD-1 antibody treatment, although production of the other Th1 and inflammatory mediators declined...
December 3, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#12
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27913228/pd-l1-immunohistochemistry-assays-for-lung-cancer-results-from-phase-1-of-the-blueprint-pd-l1-ihc-assay-comparison-project
#13
Fred R Hirsch, Abigail McElhinny, Dave Stanforth, James Ranger-Moore, Malinka Jansson, Karina Kulangara, William Richardson, Penny Towne, Debra Hanks, Bharathi Vennapusa, Amita Mistry, Rasika Kalamegham, Steve Averbuch, James Novotny, Eric Rubin, Kenneth Emancipator, Ian McCaffery, J Andrew Williams, Jill Walker, John Longshore, Ming S Tsao, Keith M Kerr
BACKGROUND: The "Blueprint PD-L1 IHC Assay Comparison Project" is an industrial-academic collaborative partnership to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials. METHODS: 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP 142 and SP 263) as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity...
November 29, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27912829/immunotherapy-in-lung-cancer
#14
REVIEW
Lingling Du, Roy S Herbst, Daniel Morgensztern
The treatment of patients with good performance status and advanced stage non-small cell lung cancer has been based on the use of first-line platinum-based doublet and second-line docetaxel. Immunotherapy represents a new therapeutic approach with the potential for prolonged benefit. Although the vaccines studied have not shown benefit in patients with non-small cell lung cancer, immune checkpoint inhibitors against the PD-1/PD-L1 axis showed increased overall survival compared with docetaxel in randomized clinical trials, which led to the approval of nivolumab and pembrolizumab...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#15
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#16
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910704/the-safety-of-nivolumab-for-the-treatment-of-advanced-non-small-cell-lung-cancer
#17
Giulio Metro, Biagio Ricciuti, Marta Brambilla, Sara Baglivo, Irene Soli, Elisa Minenza, Giulia Costanza Leonardi, Alessandro D'Arpino, Daniela Colabrese, Marco Tazza, Daniela Zicari, Vincenzo Minotti, Rita Chiari
Immune checkpoint blockaders (ICBs) act by unbalancing the immune system, thus favoring the development of an immune-mediated antitumor effect. ICBs targeting the programmed cell death receptor-1 (PD-1) have recently been investigated in a number of advanced tumors, including non-small cell lung cancer (NSCLC). Nivolumab, a fully human IgG4 kappa directed against PD-1, has been the first ICB to be approved for second-line treatment of advanced NSCLC. Areas covered: In this review we focus on the clinical development of nivolumab for the treatment of advanced NSCLC, with an emphasis on its safety profile...
December 2, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27908252/the-combination-of-new-immunotherapy-and-radiotherapy-a-new-potential-treatment-for-locally-advanced-non-small-cell-lung-cancer
#18
Paola Claudia Sacco, Paolo Maione, Cesare Guida, Cesare Gridelli
Lung cancer is the main reason of cancer death worldwide. About 30% of non-small-cell lung cancer (NSCLC) cases are diagnosed with locally advanced disease (stage III). This is a mixed population including patients who have far more extensive and bulky disease than others. Management of these patients continue to be a challenge; frequently, patients have both local recurrence and distant metastases in this stage and the prognosis is very poor with a 5-year overall survival estimated between 3% and 7% for inoperable disease...
December 1, 2016: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/27903674/atezolizumab-a-pd-l1-blocking-antibody-for-bladder-cancer
#19
Brant A Inman, Thomas A Longo, Sundhar Ramalingam, Michael R Harrison
Atezolizumab (Tecentriq™, MPDL3280A) is an FcγR-binding deficient, fully humanized, IgG1 monoclonal antibody designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironement and consequently increases T cell mediated immunity against the tumor. Atezolizumab has been FDA-approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase 2 trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27903604/what-does-pd-l1-positive-or-negative-mean
#20
Antoni Ribas, Siwen Hu-Lieskovan
Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti-PD-1/L1 antibodies. The expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence or absence. PD-L1 positivity may be a result of genetic events leading to constitutive PD-L1 expression on cancer cells or inducible PD-L1 expression on cancer cells and noncancer cells in response to a T cell infiltrate. A tumor may be PD-L1 negative because it has no T cell infiltrate, which may be reversed with an immune response...
November 30, 2016: Journal of Experimental Medicine
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