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Nivolumab renal cell carcinoma

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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/27879974/nivolumab-dose-selection-challenges-opportunities-and-lessons-learned-for-cancer-immunotherapy
#2
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/27835047/cabozantinib-for-the-treatment-of-renal-cell-carcinoma
#3
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/27741091/analysis-of-the-abscopal-effect-with-anti-pd1-therapy-in-patients-with-metastatic-solid-tumors
#4
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/27695530/nivolumab-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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/27613167/the-wide-experience-of-the-sequential-therapy-for-patients-with-metastatic-renal-cell-carcinoma
#12
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
#13
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
https://www.readbyqxmd.com/read/27557786/evaluation-of-immunogenicity-of-nivolumab-monotherapy-and-its-clinical-relevance-in-patients-with-metastatic-solid-tumors
#14
Shruti Agrawal, Paul Statkevich, Gaurav Bajaj, Yan Feng, Sally Saeger, Dharmesh D Desai, Jong-Soon Park, Ian M Waxman, Amit Roy, Manish Gupta
Nivolumab is a fully human IgG4 monoclonal antibody targeting the programmed death-1 (PD-1) receptor that blocks interactions between PD-1 and its ligands on tumor cells to prevent T cell exhaustion in patients with cancer. It has demonstrated efficacy in multiple tumor types including, melanoma, non-small cell lung cancer, and renal cell carcinoma. This analysis assessed the immunogenicity of nivolumab and its impact on pharmacokinetics, safety, and efficacy in patients with solid tumors enrolled in 6 clinical studies...
August 25, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27554835/nivolumab-induced-pericardial-tamponade-a-case-report-and-discussion
#15
Igal Kushnir, Ido Wolf
Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015...
August 24, 2016: Cardiology
https://www.readbyqxmd.com/read/27548326/an-update-on-the-pharmacodynamics-pharmacokinetics-safety-and-clinical-efficacy-of-nivolumab-in-the-treatment-of-solid-cancers
#16
Ashley C Y Wong, Brigette Ma
INTRODUCTION: Nivolumab is a programmed cell death 1 (PD-1) inhibitor that has been approved for treatment of advanced melanoma, non-small cell lung carcinoma, renal cell carcinoma and classical Hodgkin's lymphoma. AREAS COVERED: This review summarizes the latest evidence on nivolumab's pharmacodynamics, pharmacokinetics, safety and clinical efficacy in different solid tumors, based on published studies and abstracts from international conferences. EXPERT OPINION: Multiple high-level evidence has confirmed the efficacy and safety of nivolumab in solid tumors...
October 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27540850/incidence-of-programmed-cell-death-1-inhibitor-related-pneumonitis-in-patients-with-advanced-cancer-a-systematic-review-and-meta-analysis
#17
Mizuki Nishino, Anita Giobbie-Hurder, Hiroto Hatabu, Nikhil H Ramaiya, F Stephen Hodi
Importance: Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens. Objective: To compare the incidence of PD-1 inhibitor-related pneumonitis among different tumor types and therapeutic regimens. Data Sources: A PubMed search through November 10, 2015, and a review of references from relevant articles...
August 18, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27539246/emerging-monoclonal-antibodies-for-the-treatment-of-renal-cell-carcinoma-rcc
#18
Michael B Atkins, George K Philips
INTRODUCTION: Advanced renal cell carcinoma (RCC) was considered refractory to most cancer therapies until the 1980s, after which immune modulating agents and targeted agents were developed. Recently the rapid development of therapeutic monoclonal antibodies targeting immune checkpoint pathways has provided significant clinical benefit in patients with many distinct cancer types. Nivolumab, an anti-PD1 monoclonal antibody showed improvement in response rate and overall survival in patients with previously treated RCC and received US FDA approval in late 2015...
September 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27538576/tumor-mutational-load-and-immune-parameters-across-metastatic-renal-cell-carcinoma-risk-groups
#19
Guillermo de Velasco, Diana Miao, Martin H Voss, A Ari Hakimi, James J Hsieh, Nizar M Tannir, Pheroze Tamboli, Leonard J Appleman, W Kimryn Rathmell, Eliezer M Van Allen, Toni K Choueiri
Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared with patients with favorable or intermediate risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups...
October 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27533501/immunotherapy-in-kidney-cancer-the-past-present-and-future
#20
Hans Hammers
PURPOSE OF REVIEW: Kidney cancer, in particular clear cell renal cell carcinoma (ccRCC) has long been considered to be sensitive to immunotherapies. With the recent breakthroughs in immunotherapy for solid tumors and the recent approval of the first immune checkpoint inhibitor for ccRCC, we are reviewing the history of immunotherapy in kidney cancer, describing its current state and look into the future of a rapidly evolving landscape in immunotherapy for kidney cancer. RECENT FINDINGS: Systemic treatment options over the past decade have been dominated by targeted therapies inhibiting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways...
November 2016: Current Opinion in Urology
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