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https://www.readbyqxmd.com/read/28923537/metagenomic-shotgun-sequencing-and-unbiased-metabolomic-profiling-identify-specific-human-gut-microbiota-and-metabolites-associated-with-immune-checkpoint-therapy-efficacy-in-melanoma-patients
#1
Arthur E Frankel, Laura A Coughlin, Jiwoong Kim, Thomas W Froehlich, Yang Xie, Eugene P Frenkel, Andrew Y Koh
This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients. Whereas many melanoma patients exhibit profound response to ICT, there are fewer options for patients failing ICT-particularly with BRAF-wild-type disease. In preclinical studies, specific gut microbiota promotes regression of melanoma in mice. We therefore conducted a study of the effects of pretreatment gut microbiota and metabolites on ICT Response Evaluation Criteria in Solid Tumors response in 39 metastatic melanoma patients treated with ipilimumab, nivolumab, ipilimumab plus nivolumab (IN), or pembrolizumab (P)...
September 14, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28923212/a-molecular-and-preclinical-comparison-of-the-pd-1-targeted-t-cell-checkpoint-inhibitors-nivolumab-and-pembrolizumab
#2
REVIEW
Petros Fessas, Hassal Lee, Shinji Ikemizu, Tobias Janowitz
T-cell checkpoint inhibition has a profound impact on cancer care and the programmed cell death protein 1 (PD-1)-targeted antibodies nivolumab and pembrolizumab have been two of the lead molecules of this therapeutic revolution. Their clinical comparability is a highly relevant topic of discussion, but to a significant degree is a consequence of their molecular properties. Here we provide a molecular, preclinical, and early clinical comparison of the two antibodies, based on the available data and recent literature...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28923211/nivolumab-and-pembrolizumab-monoclonal-antibodies-against-programmed-cell-death-1-pd-1-that-are-interchangeable
#3
REVIEW
Vinay Prasad, Victoria Kaestner
Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28923100/checkpoint-inhibitor-is-active-against-large-cell-neuroendocrine-carcinoma-with-high-tumor-mutation-burden
#4
Victoria E Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal, David Jablons
BACKGROUND: Large cell neuroendocrine tumor (LCNEC) of the lung is a rare and aggressive tumor similar to small cell lung cancer (SCLC). Thus, it is often treated similarly to SCLC in the front-line setting with a platinum doublet. However, treatment for patients beyond the first line remains undefined. CASE PRESENTATION: We report the case of a patient with stage IB LCNEC (PD-L1 negative but positive for PD-L1 amplification and tumor mutation burden high) who progressed after adjuvant chemotherapy after surgery and subsequent therapy with an antibody drug conjugate targeting a neuroendocrine-specific cell surface marker but achieved a significant and durable response with pembrolizumab, a humanized IgG4 monoclonal anti-PD-1 antibody...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28921644/clinical-pharmacology-considerations-for-the-development-of-immune-checkpoint-inhibitors
#5
Jennifer Sheng, Shivani Srivastava, Kinjal Sanghavi, Zheng Lu, Brian J Schmidt, Akintunde Bello, Manish Gupta
Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28919706/profile-of-pembrolizumab-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma-design-development-and-place-in-therapy
#6
REVIEW
Sulsal Haque, Mahender Yellu, Jaskirat Randhawa, Nooshin Hashemi-Sadraei
Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#7
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28915714/the-efficacy-of-anti-pd-1-pd-l1-therapy-and-its-comparison-with-egfr-tkis-for-advanced-non-small-cell-lung-cancer
#8
REVIEW
Zhixin Sheng, Xu Zhu, Yanhua Sun, Yanxia Zhang
PURPOSE: To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). METHODS: The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. RESULTS: Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913853/dose-rationalisation-of-pembrolizumab-and-nivolumab-using-pharmacokinetic-modelling-and-simulation-and-cost-analysis
#9
Kayode Ogungbenro, Alkesh Patel, Robert Duncombe, Richard Nuttall, James Clark, Paul Lorigan
Pembrolizumab and nivolumab are highly selective anti PD-1 antibodies approved for the treatment of advanced malignancies. Variable exposure and significant wastage have been associated with body size dosing of monoclonal antibodies. The following dosing strategies were evaluated using simulations: body weight, dose banding, fixed dose and pharmacokinetics based method. The relative cost to body weight dosing for band, fixed 150 mg and 200 mg, and pharmacokinetics derived strategies were -15%, -25%, +7% and -16% for pembrolizumab and -8%, -6%, and -10% for band, fixed, and pharmacokinetics derived strategies for nivolumab...
September 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28899972/facts-and-hopes-in-immunotherapy-of-lymphoma-and-myeloma
#10
Matthew J Pianko, Alison J Moskowitz, Alexander M Lesokhin
Immune checkpoint blockade has driven a revolution in modern oncology, and robust drug development of immune checkpoint inhibitors is underway in both solid tumors and hematologic malignancies. High response rates to programmed cell death 1 (PD-1) blockade using nivolumab or pembrolizumab in classical Hodgkin lymphoma (cHL) and several variants of non-Hodgkin lymphoma (NHL) revealed an intrinsic biologic sensitivity to this approach, and work is ongoing exploring combinations with immune checkpoint inhibitors in both cHL and NHL...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28889921/pd-1-checkpoint-inhibition-toxicities-and-management
#11
REVIEW
Andrew W Hahn, David M Gill, Neeraj Agarwal, Benjamin L Maughan
PURPOSE: With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. MATERIALS AND METHODS: In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab...
September 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28886381/oncolytic-virotherapy-promotes-intratumoral-t-cell-infiltration-and-improves-anti-pd-1-immunotherapy
#12
Antoni Ribas, Reinhard Dummer, Igor Puzanov, Ari VanderWalde, Robert H I Andtbacka, Olivier Michielin, Anthony J Olszanski, Josep Malvehy, Jonathan Cebon, Eugenio Fernandez, John M Kirkwood, Thomas F Gajewski, Lisa Chen, Kevin S Gorski, Abraham A Anderson, Scott J Diede, Michael E Lassman, Jennifer Gansert, F Stephen Hodi, Georgina V Long
Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28883738/checkpoint-inhibitors-for-malignant-melanoma-a-systematic-review-and-meta-analysis
#13
REVIEW
Adam K Karlsson, Sohag N Saleh
BACKGROUND AND OBJECTIVES: Rates of malignant melanoma are continuing to increase, and until recently effective treatments were lacking. However, since 2011 three immunotherapeutic agents, known as checkpoint inhibitors, have been approved. This review aims to establish whether these three drugs - ipilimumab, nivolumab, and pembrolizumab - offer greater efficacy and tolerability compared to control interventions (placebo, immunotherapy, or chemotherapy) in patients with stage III or IV unresectable cutaneous melanoma...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28883282/development-of-immune-checkpoint-inhibitors
#14
Shigehisa Kitano
Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28881222/immune-checkpoint-blockade-for-unresectable-or-metastatic-uveal-melanoma-a-systematic-review
#15
REVIEW
Markus V Heppt, Theresa Steeb, Justin Gabriel Schlager, Stefanie Rosumeck, Corinna Dressler, Thomas Ruzicka, Alexander Nast, Carola Berking
BACKGROUND: The use of immune checkpoint blockade (ICB) for uveal melanoma (UM) is little established. The aim of this review was to provide a comprehensive overview on the efficacy, safety, and tolerability of ICB in patients with UM. METHODS: We performed a systematic literature research covering MEDLINE, Embase and CENTRAL. Abstracts of pertinent conferences and trial registers were handsearched for relevant studies. RESULTS: Out of 1327 records initially identified, 12 eligible studies were included in the qualitative synthesis...
August 24, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28880747/pembrolizumab-in-programmed-death-ligand-1-positive-endometrial-cancer
#16
Federica Tomao, Pierluigi Benedetti Panici, Silverio Tomao
No abstract text is available yet for this article.
September 7, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28879076/immunotherapy-shock-a-case-series-of-pd-l1-100-and-pembrolizumab-first-line-treatment
#17
Paul Zarogoulidis, Evaggelia Athanasiou, Theodora Tsiouda, Dimitrios Hatzibougias, Haidong Huang, Chong Bai, Georgia Trakada, Lemonia Veletza, Anastasios Kallianos, Christoforos Kosmidis, Nikolaos Barbetakis, Dimitrios Paliouras, Aggeliki Rapti, Dimitrios Drougas, Wolfgang Hohenforst-Schmidt
In this decade a "bloom" of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28878661/the-successful-treatment-of-pulmonary-pleomorphic-carcinoma-with-pembrolizumab-a-case-report
#18
Yoko Matsumoto, Tamaki Miura, Hajime Horiuchi, Kazuhiro Usui
Pulmonary pleomorphic carcinomas are rare malignant tumors, and no standard treatments have been established. We herein report the successful treatment of a patient with pulmonary pleomorphic carcinoma with pembrolizumab. A 51-year-old man who was a current smoker presented to our hospital due to dyspnea and hemosputum. Chest X-ray showed right-sided pneumothorax with pleural effusion; chest tube drainage was therefore performed. Computed tomography after chest tube drainage showed a cavitary nodule in the right upper lobe and right hilar and bilateral mediastinal lymphadenopathy...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28877632/case-report-pembrolizumab-induced-type-1-diabetes-in-a-patient-with-metastatic-cholangiocarcinoma
#19
Matthew A Smith-Cohn, David Gill, Benjamin N Voorhies, Neeraj Agarwal, Ignacio Garrido-Laguna
BACKGROUND:  Immune checkpoint inhibitors are novel cancer therapies associated with numerous autoimmune toxicities, some of which are only now being appreciated. CASE PRESENTATION:  A 67-year old female with metastatic cholangiocarcinoma and no prior history of diabetes was treated with leucovorin, fluorouracil, oxaliplatin and pembrolizumab. After eight cycles, she developed new onset type 1 diabetes mellitus with positive glutamic acid decarboxylase antibody titers...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/28877075/microsatellite-instability-a-predictive-biomarker-for-cancer-immunotherapy
#20
Liisa Chang, Minna Chang, Hanna M Chang, Fuju Chang
Immunotherapy has shown promising results in various types of cancers. Checkpoint inhibitor drugs developed for cancer immunotherapy have been approved by the US Food and Drug Administration (FDA) for patients with advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma. In the latest announcement, the FDA has granted accelerated approval to pembrolizumab for pediatric and adult patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient solid tumors...
September 4, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
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