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Nivolumab and renal

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https://www.readbyqxmd.com/read/27921007/long-term-response-to-nivolumab-and-acute-renal-failure-in-a-patient-with-metastatic-papillary-renal-cell-carcinoma-and-a-pd-l1-tumor-expression-increased-with-sunitinib-therapy-a-case-report
#1
Juan Ruiz-Bañobre, Urbano Anido, Ihab Abdulkader, José Antúnez-López, Rafael López-López, Jorge García-González
INTRODUCTION: Papillary renal cell carcinoma (PRCC), which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal cell carcinoma...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27920704/autoimmune-hemolytic-anemia-as-a-complication-of-nivolumab-therapy
#2
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/27879974/nivolumab-dose-selection-challenges-opportunities-and-lessons-learned-for-cancer-immunotherapy
#3
Shruti Agrawal, Yan Feng, Amit Roy, Georgia Kollia, Brian Lestini
BACKGROUND: Immuno-oncology (I-O) therapies target the host immune system, providing the potential to choose a uniform dose and schedule across tumor types. However, dose selection for I-O agents usually occurs early in clinical development and is typically based on tumor response, which may not fully represent the potential for improved overall survival. Here, we describe an integrated approach which incorporates clinical safety and efficacy data with data obtained from analyses of dose-/exposure-response (D-R/E-R) relationships, used to select a monotherapy dose for nivolumab, a programmed death-1 inhibitor, in clinical studies of different tumor types...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27857838/hyponatraemia-secondary-to-nivolumab-induced-primary-adrenal-failure
#4
Harris Trainer, Paul Hulse, Claire E Higham, Peter Trainer, Paul Lorigan
: Checkpoint inhibitors, such as ipilimumab and pembrolizumab, have transformed the prognosis for patients with advanced malignant melanoma and squamous non-small-cell lung cancer, and their use will only expand as experience is gained in a variety of other malignancies, for instance, renal and lymphoma. As the use of checkpoint inhibitors increases, so too will the incidence of their unique side effects, termed immune-related adverse events (irAEs), which can affect dermatological, gastrointestinal, hepatic, endocrine and other systems...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27843624/the-european-society-for-medical-oncology-magnitude-of-clinical-benefit-scale-in-daily-practice-a-single-institution-real-life-experience-at-the-medical-university-of-vienna
#5
Barbara Kiesewetter, Markus Raderer, Günther G Steger, Rupert Bartsch, Robert Pirker, Sabine Zöchbauer-Müller, Gerald Prager, Michael Krainer, Matthias Preusser, Manuela Schmidinger, Christoph C Zielinski
BACKGROUND: The European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) has been designed to stratify the therapeutic benefit of a certain drug registered for the treatment of cancer. However, though internally validated, this tool has not yet been evaluated for its feasibility in the daily practice of a major center of medical oncology. METHODS: The practicability of the MCBS for advanced oncological diseases at the Clinical Division of Oncology, Medical University of Vienna, which constitutes one of the largest oncological centres in Europe, was analysed in a three-step approach...
2016: ESMO Open
https://www.readbyqxmd.com/read/27835047/cabozantinib-for-the-treatment-of-renal-cell-carcinoma
#6
Bernard Escudier, Julie C Lougheed, Laurence Albiges
Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy...
November 22, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27832664/acute-interstitial-nephritis-related-to-immune-checkpoint-inhibitors
#7
Julie Belliere, Nicolas Meyer, Julien Mazieres, Sylvie Ollier, Serge Boulinguez, Audrey Delas, David Ribes, Stanislas Faguer
BACKGROUND: Immune checkpoint inhibitors (anti-PD1 or anti-CTLA-4) are increasingly used in various cancers. Immune checkpoint inhibitors (ICI)-related renal disorders are poorly described (9 cases) and were only related to Ipilimumab. METHODS: Retrospective collection of clinical charts of all the patients admitted for renal disorders following ICI in the University Hospital of Toulouse (France). RESULTS: We report on adverse renal events that occurred in three patients treated with anti-PD1 (nivolumab or pembrolizumab) or anti-CTLA-4 (ipilimumab)...
November 10, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27777773/antitumor-activity-of-nivolumab-on-hemodialysis-after-renal-allograft-rejection
#8
Michael Ong, Andrea Marie Ibrahim, Samuel Bourassa-Blanchette, Christina Canil, Todd Fairhead, Greg Knoll
BACKGROUND: Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27741091/analysis-of-the-abscopal-effect-with-anti-pd1-therapy-in-patients-with-metastatic-solid-tumors
#9
Jéssica Ribeiro Gomes, Rafael A Schmerling, Carolina K Haddad, Douglas J Racy, Robson Ferrigno, Erlon Gil, Pedro Zanuncio, Antônio C Buzaid
Abscopal effect is a rare phenomenon characterized by tumor regression of untreated metastatic lesions after a local therapy (eg, radiotherapy). We studied the probability of abscopal effect with radiotherapy associated with anti-programmed death cell 1 (PD1) therapy after progression on anti-PD1. This study is a retrospective analysis of patients treated with nivolumab or pembrolizumab for melanoma, non-small cell lung cancer (NSCLC) and renal cancer at Antônio Ermírio de Moraes Oncology Center, Brazil. To be eligible for this analysis, patients must have had unequivocal evidence of disease progression on anti-PD1 therapy and subsequent radiotherapy for any tumor site while still receiving anti-PD1...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27733243/nivolumab-monotherapy-in-recurrent-metastatic-urothelial-carcinoma-checkmate-032-a-multicentre-open-label-two-stage-multi-arm-phase-1-2-trial
#10
Padmanee Sharma, Margaret K Callahan, Petri Bono, Joseph Kim, Pavlina Spiliopoulou, Emiliano Calvo, Rathi N Pillai, Patrick A Ott, Filippo de Braud, Michael Morse, Dung T Le, Dirk Jaeger, Emily Chan, Chris Harbison, Chen-Sheng Lin, Marina Tschaika, Alex Azrilevich, Jonathan E Rosenberg
BACKGROUND: Few effective treatments exist for patients with advanced urothelial carcinoma that has progressed after platinum-based chemotherapy. We assessed the activity and safety of nivolumab in patients with locally advanced or metastatic urothelial carcinoma whose disease progressed after previous platinum-based chemotherapy. METHODS: In this phase 1/2, multicentre, open-label study, we enrolled patients (age ≥18 years) with urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra at 16 sites in Finland, Germany, Spain, the UK, and the USA...
October 7, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27695530/nivolumab-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#11
Alessia Mennitto, Paolo Grassi, Raffaele Ratta, Elena Verzoni, Michele Prisciandaro, Giuseppe Procopio
Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α)...
October 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27690664/emerging-growth-factor-receptor-antagonists-for-the-treatment-of-renal-cell-carcinoma
#12
Haris Zahoor, Brian I Rini
The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas Covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials, which led to their approval, is presented...
October 3, 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27683031/the-efficacy-and-safety-of-anti-pd-1-pd-l1-antibodies-for-treatment-of-advanced-or-refractory-cancers-a-meta-analysis
#13
Tengfei Zhang, Jing Xie, Seiji Arai, Liping Wang, Xuezhong Shi, Ni Shi, Fen Ma, Sen Chen, Lan Huang, Li Yang, Wang Ma, Bin Zhang, Weidong Han, Jianchuan Xia, Hu Chen, Yi Zhang
PURPOSE: To systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer. RESULTS: Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53-2.41), 21% (95% CI: 17%-25%) and 21% (95% CI: 16%-27%) respectively. While the overall adverse effects rate for melanoma, NSCLC, RCC were 16% (95% CI: 6%-28%), 11% (95% CI: 8%-14%) and 20% (95% CI: 11%-32%) respectively...
September 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27680188/-immunooncology-in-urologic-cancers-current-status
#14
M-O Grimm
Immune checkpoint inhibitors are establishing itselves as a new systemic treatment option (in addition to chemotherapy and targeted therapy) for metastatic tumours. (Re)activating the immune system, these antibodies may lead to impressive remissions lasting for a long time in some patients. Regarding urological tumours, the anti-PD-1 antibody Nivolumab (Opdivo(®)) has been approved this year for advanced, previously treated renal cell carcinoma. In the United States, Atezolizumab (Tecentriq(®)) has been approved for metastatic urothelial carcinoma after platinum-based chemotherapy...
September 2016: Aktuelle Urologie
https://www.readbyqxmd.com/read/27667773/an-analytical-comparison-of-dako-28-8-pharmdx-assay-and-an-e1l3n-laboratory-developed-test-in-the-immunohistochemical-detection-of-programmed-death-ligand-1
#15
John Cogswell, H David Inzunza, Qiuyan Wu, John N Feder, Gabe Mintier, James Novotny, Diana M Cardona
AIM: Nivolumab, a fully human immunoglobulin G4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has activity in melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and Hodgkin lymphoma. Nivolumab is approved in the USA and EU for advanced melanoma, NSCLC, and RCC, and relapsed Hodgkin lymphoma in the USA. Programmed death-ligand 1 (PD-L1), a PD-1 ligand, is expressed on mononuclear leukocytes, myeloid cells, and tumor cells. PD-L1 is being investigated as a potential biomarker to predict the association of tumor PD-L1 expression with nivolumab efficacy...
September 26, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27664394/improvement-in-survival-end-points-of-patients-with-metastatic-renal-cell-carcinoma-through-sequential-targeted-therapy
#16
Emiliano Calvo, Manuela Schmidinger, Daniel Y C Heng, Viktor Grünwald, Bernard Escudier
Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab...
September 10, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27621699/everolimus-in-the-management-of-metastatic-renal-cell-carcinoma-an-evidence-based-review-of-its-place-in-therapy
#17
REVIEW
Sebastiano Buti, Alessandro Leonetti, Alice Dallatomasina, Melissa Bersanelli
INTRODUCTION: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, and its pathogenesis is strictly related to altered cellular response to hypoxia, in which mTOR signaling pathway is implicated. Everolimus, an mTOR serine/threonine kinase inhibitor, represents a therapeutic option for the treatment of advanced RCC. AIM: The objective of this article is to review the evidence for the treatment of metastatic RCC with everolimus. EVIDENCE REVIEW: Everolimus was approved for second- and third-line therapy in patients with advanced RCC according to the results of a Phase III pivotal trial that demonstrated a benefit in median progression-free survival of ~2 months compared to placebo after failure of previous lines of therapy, of which at least one was an anti-VEGFR tyrosine kinase inhibitor (TKI)...
2016: Core Evidence
https://www.readbyqxmd.com/read/27614165/checkpoint-inhibitors-in-chronic-kidney-failure-and-an-organ-transplant-recipient
#18
Saskia Herz, Thomas Höfer, Matina Papapanagiotou, Julia Christina Leyh, Sarah Meyenburg, Dirk Schadendorf, Selma Ugurel, Alexander Roesch, Elisabeth Livingstone, Bastian Schilling, Cindy Franklin
BACKGROUND: Immune-checkpoint inhibitors have been approved for the treatment of metastatic melanoma based on several phase III trials. Patients after organ transplantation and patients with impaired renal function were excluded from these studies. Recently, allograft rejections were reported in organ transplant recipients receiving PD-1 blocking antibodies. PATIENTS AND FINDINGS: Four patients with metastatic melanoma and impaired kidney function (baseline serum creatinine 1...
November 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27613167/the-wide-experience-of-the-sequential-therapy-for-patients-with-metastatic-renal-cell-carcinoma
#19
REVIEW
Julio Lambea, Urbano Anido, Olatz Etxániz, Luis Flores, Álvaro Montesa, Juan Manuel Sepúlveda, Emilio Esteban
Sequential targeted therapies are the standard of care for patients with metastatic renal cell carcinoma (mRCC). Several drugs are available for patients whose disease progresses while they receive initial tyrosine kinase inhibitor (TKI) therapy; these include nivolumab (an inhibitor of PD-1 receptor), everolimus (an inhibitor of the mechanistic target of rapamycin) or additional TKIs. Until now, there has been no clinical evidence to support the use of one strategy versus another, so investigators and physicians rely on experience, judgement and findings from molecular analyses to select the appropriate treatment...
November 2016: Current Oncology Reports
https://www.readbyqxmd.com/read/27563657/immunobiology-and-immunotherapy-in-genitourinary-malignancies
#20
REVIEW
Marinos Tsiatas, Petros Grivas
Immunotherapy has traditionally been a critical component of the cancer treatment armamentarium in genitourinary (GU) cancers. It has an established role in the management of carefully selected patients with metastatic renal cell carcinoma (RCC) [e.g., high dose interleukin-2 (IL-2)] and non-muscle invasive bladder cancer (NMIBC) [e.g., intravesical Bacillus Calmette-Guérin (BCG)]. In 2010, the sipuleucel-T vaccine was approved by the FDA for the management of metastatic castration-resistant prostate cancer (mCRPC), based on a phase III trial showing overall survival (OS) benefit compared to placebo...
July 2016: Annals of Translational Medicine
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