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https://www.readbyqxmd.com/read/29217585/patient-hla-class-i-genotype-influences-cancer-response-to-checkpoint-blockade-immunotherapy
#1
Diego Chowell, Luc G T Morris, Claud M Grigg, Jeffrey K Weber, Robert M Samstein, Vladimir Makarov, Fengshen Kuo, Sviatoslav M Kendall, David Requena, Nadeem Riaz, Benjamin Greenbaum, James Carroll, Edward Garon, David M Hyman, Ahmet Zehir, David Solit, Michael Berger, Ruhong Zhou, Naiyer A Rizvi, Timothy A Chan
CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-PD-1 or anti-CTLA-4 is currently unknown. We determined the HLA-I genotype of 1,535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (A, B, and C) improved overall survival after ICB compared to patients who were homozygous for at least one HLA locus...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29141165/immunotherapy-for-unresectable-stage-iii-non-small-cell-lung-cancer
#2
EDITORIAL
Naiyer A Rizvi, Solange Peters
New England Journal of Medicine, Volume 377, Issue 20, Page 1986-1988, November 2017.
November 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29132144/a-neoantigen-fitness-model-predicts-tumour-response-to-checkpoint-blockade-immunotherapy
#3
Marta Łuksza, Nadeem Riaz, Vladimir Makarov, Vinod P Balachandran, Matthew D Hellmann, Alexander Solovyov, Naiyer A Rizvi, Taha Merghoub, Arnold J Levine, Timothy A Chan, Jedd D Wolchok, Benjamin D Greenbaum
Checkpoint blockade immunotherapies enable the host immune system to recognize and destroy tumour cells. Their clinical activity has been correlated with activated T-cell recognition of neoantigens, which are tumour-specific, mutated peptides presented on the surface of cancer cells. Here we present a fitness model for tumours based on immune interactions of neoantigens that predicts response to immunotherapy. Two main factors determine neoantigen fitness: the likelihood of neoantigen presentation by the major histocompatibility complex (MHC) and subsequent recognition by T cells...
November 23, 2017: Nature
https://www.readbyqxmd.com/read/29024471/programmed-death-ligand-1-expression-in-non-small-cell-lung-carcinoma-comparison-among-cytology-small-biopsy-and-surgical-resection-specimens
#4
Jonas J Heymann, William A Bulman, David Swinarski, Carlos A Pagan, John P Crapanzano, Mehrvash Haghighi, Ladan Fazlollahi, Mark B Stoopler, Joshua R Sonett, Adrian G Sacher, Catherine A Shu, Naiyer A Rizvi, Anjali Saqi
BACKGROUND: One immunotherapeutic agent for patients with advanced non-small cell lung carcinoma, pembrolizumab, has a companion immunohistochemistry (IHC)-based assay that predicts response by quantifying programmed death-ligand 1 (PD-L1) expression. The current study assessed the feasibility of quantifying PD-L1 expression using cytologic non-small cell lung carcinoma specimens and compared the results with those from small biopsy and surgical resection specimens. METHODS: PD-L1 expression was quantified using the IHC-based 22C3 pharmDx assay, with "positivity" defined as staining in ≥50% viable tumor cells; ≥ 100 tumor cells were required for test adequacy...
October 12, 2017: Cancer
https://www.readbyqxmd.com/read/29023213/nivolumab-versus-docetaxel-in-previously-treated-patients-with-advanced-non-small-cell-lung-cancer-two-year-outcomes-from-two-randomized-open-label-phase-iii-trials-checkmate-017-and-checkmate-057
#5
RANDOMIZED CONTROLLED TRIAL
Leora Horn, David R Spigel, Everett E Vokes, Esther Holgado, Neal Ready, Martin Steins, Elena Poddubskaya, Hossein Borghaei, Enriqueta Felip, Luis Paz-Ares, Adam Pluzanski, Karen L Reckamp, Marco A Burgio, Martin Kohlhäeufl, David Waterhouse, Fabrice Barlesi, Scott Antonia, Oscar Arrieta, Jérôme Fayette, Lucio Crinò, Naiyer Rizvi, Martin Reck, Matthew D Hellmann, William J Geese, Ang Li, Anne Blackwood-Chirchir, Diane Healey, Julie Brahmer, Wilfried E E Eberhardt
Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies. Methods Patients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks)...
December 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28609226/phase-ii-trial-of-atezolizumab-as-first-line-or-subsequent-therapy-for-patients-with-programmed-death-ligand-1-selected-advanced-non-small-cell-lung-cancer-birch
#6
MULTICENTER STUDY
Solange Peters, Scott Gettinger, Melissa L Johnson, Pasi A Jänne, Marina C Garassino, Daniel Christoph, Chee Keong Toh, Naiyer A Rizvi, Jamie E Chaft, Enric Carcereny Costa, Jyoti D Patel, Laura Q M Chow, Marianna Koczywas, Cheryl Ho, Martin Früh, Michel van den Heuvel, Jeffrey Rothenstein, Martin Reck, Luis Paz-Ares, Frances A Shepherd, Takayasu Kurata, Zhengrong Li, Jiaheng Qiu, Marcin Kowanetz, Simonetta Mocci, Geetha Shankar, Alan Sandler, Enriqueta Felip
Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled...
August 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28398273/the-use-of-immunotherapy-in-the-first-line-treatment-of-lung-cancer
#7
Naiyer A Rizvi
No abstract text is available yet for this article.
March 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28211505/corrigendum-defining-a-radiomic-response-phenotype-a-pilot-study-using-targeted-therapy-in-nsclc
#8
Hugo J W L Aerts, Patrick Grossmann, Yongqiang Tan, Geoffrey R Oxnard, Naiyer Rizvi, Lawrence H Schwartz, Binsheng Zhao
No abstract text is available yet for this article.
February 17, 2017: Scientific Reports
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
#9
RANDOMIZED CONTROLLED TRIAL
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...
January 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27686971/phase-2-study-of-erlotinib-in-combination-with%C3%A2-linsitinib-osi-906-or-placebo-in-chemotherapy-naive-patients-with-non-small-cell-lung-cancer-and-activating-epidermal-growth-factor-receptor-mutations
#10
RANDOMIZED CONTROLLED TRIAL
Natasha B Leighl, Naiyer A Rizvi, Lopes Gilberto de Lima, Wichit Arpornwirat, Charles M Rudin, Alberto A Chiappori, Myung-Ju Ahn, Laura Q M Chow, Lyudmila Bazhenova, Arunee Dechaphunkul, Patrapim Sunpaweravong, Keith Eaton, Jihong Chen, Sonja Medley, Srinivasu Poondru, Margaret Singh, Joyce Steinberg, Rosalyn A Juergens, Shirish M Gadgeel
INTRODUCTION: First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment of advanced non-small-cell lung cancer with EGFR-activating mutations improves outcomes compared with chemotherapy, but resistance develops in most patients. Compensatory signaling through type 1 insulin-like growth factor 1 receptor (IGF-1R) may contribute to resistance; dual blockade of IGF-1R and EGFR may improve outcomes. PATIENTS AND METHODS: We performed a randomized, double-blind, placebo-controlled phase II study of linsitinib, a dual IGF-1R and insulin receptor tyrosine kinase inhibitor, plus erlotinib versus placebo plus erlotinib in chemotherapy-naive patients with EGFR-mutation positive, advanced non-small-cell lung cancer...
January 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27676569/p2-35-nivolumab-vs-docetaxel-in-advanced%C3%A2-nsclc-checkmate-017-057%C3%A2-2-y-update-and-exploratory-cytokine-profile-analysis-track-immunotherapy
#11
Hossein Borghaei, Julie Brahmer, Leora Horn, Neal Ready, Martin Steins, Enriqueta Felip, Luis Paz-Ares, Xx Xx, Fabrice Barlesi, Scott Antonia, Jérome Fayette, Naiyer Rizvi, Lucio Crino, Martin Reck, Wilfried Ernst Erich Eberhardt, Matthew Hellmann, Kaushal Desai, Ang Li, Diane Healey, David Spigel, Clarissa Mathias
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27645803/defining-a-radiomic-response-phenotype-a-pilot-study-using-targeted-therapy-in-nsclc
#12
Hugo J W L Aerts, Patrick Grossmann, Yongqiang Tan, Geoffrey G Oxnard, Naiyer Rizvi, Lawrence H Schwartz, Binsheng Zhao
Medical imaging plays a fundamental role in oncology and drug development, by providing a non-invasive method to visualize tumor phenotype. Radiomics can quantify this phenotype comprehensively by applying image-characterization algorithms, and may provide important information beyond tumor size or burden. In this study, we investigated if radiomics can identify a gefitinib response-phenotype, studying high-resolution computed-tomography (CT) imaging of forty-seven patients with early-stage non-small cell lung cancer before and after three weeks of therapy...
September 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27532023/pd-l1-biomarker-testing-for-non-small-cell-lung-cancer-truth-or-fiction
#13
REVIEW
Claud Grigg, Naiyer A Rizvi
Research in cancer immunology is currently accelerating following a series of cancer immunotherapy breakthroughs during the last 5 years. Various monoclonal antibodies which block the interaction between checkpoint molecules PD-1 on immune cells and PD-L1 on cancer cells have been used to successfully treat non-small cell lung cancer (NSCLC), including some durable responses lasting years. Two drugs, nivolumab and pembrolizumab, are now FDA approved for use in certain patients who have failed or progressed on platinum-based or targeted therapies while agents targeting PD-L1, atezolizumab and durvalumab, are approaching the final stages of clinical testing...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27354485/nivolumab-monotherapy-for-first-line-treatment-of-advanced-non-small-cell-lung-cancer
#14
Scott Gettinger, Naiyer A Rizvi, Laura Q Chow, Hossein Borghaei, Julie Brahmer, Neal Ready, David E Gerber, Frances A Shepherd, Scott Antonia, Jonathan W Goldman, Rosalyn A Juergens, Scott A Laurie, Faith E Nathan, Yun Shen, Christopher T Harbison, Matthew D Hellmann
PURPOSE: Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. METHODS: Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27354481/nivolumab-in-combination-with-platinum-based-doublet-chemotherapy-for-first-line-treatment-of-advanced-non-small-cell-lung-cancer
#15
Naiyer A Rizvi, Matthew D Hellmann, Julie R Brahmer, Rosalyn A Juergens, Hossein Borghaei, Scott Gettinger, Laura Q Chow, David E Gerber, Scott A Laurie, Jonathan W Goldman, Frances A Shepherd, Allen C Chen, Yun Shen, Faith E Nathan, Christopher T Harbison, Scott Antonia
PURPOSE: Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC)...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27308563/genomic-profile-smoking-and-response-to-anti-pd-1-therapy-in-non-small-cell-lung-carcinoma
#16
Matthew Hellmann, Naiyer Rizvi, Jedd D Wolchok, Timothy A Chan
The recent successes of immune checkpoint therapies have established a new era for the treatment of patients with cancer, yet the predictors of response remain largely undetermined. We recently demonstrated that the genomic landscape of lung cancers substantially influences the response to programmed cell death 1 receptor (PD-1) blockade, providing new insights into the molecular determinants of the response to immunotherapy.
January 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27092830/association-of-pembrolizumab-with-tumor-response-and-survival-among-patients-with-advanced-melanoma
#17
MULTICENTER STUDY
Antoni Ribas, Omid Hamid, Adil Daud, F Stephen Hodi, Jedd D Wolchok, Richard Kefford, Anthony M Joshua, Amita Patnaik, Wen-Jen Hwu, Jeffrey S Weber, Tara C Gangadhar, Peter Hersey, Roxana Dronca, Richard W Joseph, Hassane Zarour, Bartosz Chmielowski, Donald P Lawrence, Alain Algazi, Naiyer A Rizvi, Brianna Hoffner, Christine Mateus, Kevin Gergich, Jill A Lindia, Maxine Giannotti, Xiaoyun Nicole Li, Scot Ebbinghaus, S Peter Kang, Caroline Robert
IMPORTANCE: The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab. OBJECTIVE: To characterize the association of pembrolizumab with tumor response and overall survival among patients with advanced melanoma. DESIGN, SETTINGS, AND PARTICIPANTS: Open-label, multicohort, phase 1b clinical trials (enrollment, December 2011-September 2013). Median duration of follow-up was 21 months...
April 19, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27026678/into-the-clinic-with-nivolumab-and-pembrolizumab
#18
Catherine A Shu, Naiyer A Rizvi
No abstract text is available yet for this article.
May 2016: Oncologist
https://www.readbyqxmd.com/read/26940869/clonal-neoantigens-elicit-t-cell-immunoreactivity-and-sensitivity-to-immune-checkpoint-blockade
#19
Nicholas McGranahan, Andrew J S Furness, Rachel Rosenthal, Sofie Ramskov, Rikke Lyngaa, Sunil Kumar Saini, Mariam Jamal-Hanjani, Gareth A Wilson, Nicolai J Birkbak, Crispin T Hiley, Thomas B K Watkins, Seema Shafi, Nirupa Murugaesu, Richard Mitter, Ayse U Akarca, Joseph Linares, Teresa Marafioti, Jake Y Henry, Eliezer M Van Allen, Diana Miao, Bastian Schilling, Dirk Schadendorf, Levi A Garraway, Vladimir Makarov, Naiyer A Rizvi, Alexandra Snyder, Matthew D Hellmann, Taha Merghoub, Jedd D Wolchok, Sachet A Shukla, Catherine J Wu, Karl S Peggs, Timothy A Chan, Sine R Hadrup, Sergio A Quezada, Charles Swanton
As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+)tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer and expressed high levels of PD-1...
March 25, 2016: Science
https://www.readbyqxmd.com/read/26858122/safety-and-antitumour-activity-of-durvalumab-plus-tremelimumab-in-non-small-cell-lung-cancer-a-multicentre-phase-1b-study
#20
RANDOMIZED CONTROLLED TRIAL
Scott Antonia, Sarah B Goldberg, Ani Balmanoukian, Jamie E Chaft, Rachel E Sanborn, Ashok Gupta, Rajesh Narwal, Keith Steele, Yu Gu, Joyson J Karakunnel, Naiyer A Rizvi
BACKGROUND: PD-L1 and CTLA-4 immune checkpoints inhibit antitumour T-cell activity. Combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab might provide greater antitumour activity than either drug alone. We aimed to assess durvalumab plus tremelimumab in patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC). METHODS: We did a multicentre, non-randomised, open-label, phase 1b study at five cancer centres in the USA...
March 2016: Lancet Oncology
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