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https://www.readbyqxmd.com/read/29239194/-immunotherapy-of-renal-cell-carcinoma
#1
A Poprach, R Lakomý, T Büchler
Treatment of renal cell carcinoma is still palliative. Targeted therapy increases response rates and prolongs overall survival and progression-free survival compared with cytokines and chemotherapy. Checkpoint inhibitors constitute the up-date of therapeutic approaches, and anti-PD-1 antibody, one checkpoint inhibitor, is now well established as a second and/or third palliative treatment for patients with renal cell carcinoma. In this study, we present the latest data from current studies on cytokines, cancer vaccines, ipilimumab, and nivolumab...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29239187/-immunotherapy-for-bladder-cancer
#2
T Büchler
Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29205200/immunotherapy-in-metastatic-urothelial-carcinoma-focus-on-immune-checkpoint-inhibition
#3
REVIEW
Arlene Siefker-Radtke, Brendan Curti
Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the immunogenic potential of metastatic urothelial carcinoma have led to the accelerated FDA approval of the immune checkpoint inhibitors atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary findings suggest additional benefits of combinations of immunotherapeutic agents as a future treatment approach in metastatic urothelial carcinoma...
December 5, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29196189/pd-l1-inflammation-non-coding-rnas-and-neuroblastoma-immuno-oncology-perspective
#4
REVIEW
Palanisamy Nallasamy, Srinivas Chava, Sumit S Verma, Shruti Mishra, Santhi Gorantla, Don W Coulter, Siddappa N Byrareddy, Surinder K Batra, Subash C Gupta, Kishore B Challagundla
Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system...
November 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29194007/product-review-on-the-anti-pd-l1-antibody-atezolizumab
#5
Neil J Shah, William J Kelly, Stephen V Liu, Karin Choquette, Alexander Spira
Immunotherapy as a therapeutic strategy has seized the narrative throughout clinical oncology over the past few years. Once considered a niche treatment for rare cancers, immunotherapy has quickly emerged as the standard of care for many common cancer types. The remarkable rise is largely due to the development of novel checkpoint inhibitors, specifically, antibodies targeting PD-1 and PD-L1. Offering promising efficacy with a favorable toxicity profile, these agents have been approved for use in several malignancies and are under investigation for many more...
December 1, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29191596/pd-l1-expression-in-advanced-nsclc-insights-into-risk-stratification-and-treatment-selection-from-a-systematic-literature-review
#6
REVIEW
Robert Brody, Yiduo Zhang, Marc Ballas, Mohd Kashif Siddiqui, Palvi Gupta, Craig Barker, Anita Midha, Jill Walker
Tumors can evade immune detection by exploiting inhibitory immune checkpoints such as the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Antibodies that block this pathway offer a promising new approach to treatment in advanced/metastatic non-small cell lung cancer (NSCLC). A systematic review of the literature was conducted to assess the association of PD-L1 with important patient and disease characteristics, the prognostic significance of PD-L1 expressing NSCLC tumors, and the value of PD-L1 as a predictive biomarker of response to anti-PD-1/PD-L1 treatments in advanced/metastatic NSCLC...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29182441/elimination-of-tumor-by-cd47-pd-l1-dual-targeting-fusion-protein-that-engages-innate-and-adaptive-immune-responses
#7
Boning Liu, Huaizu Guo, Jin Xu, Ting Qin, Qingcheng Guo, Nana Gu, Dapeng Zhang, Weizhu Qian, Jianxin Dai, Sheng Hou, Hao Wang, Yajun Guo
The host immune system generally serves as a barrier against tumor formation. Programmed death-ligand 1 (PD-L1) is a critical "don't find me" signal to the adaptive immune system, whereas CD47 transmits an anti-phagocytic signal, known as the "don't eat me" signal, to the innate immune system. These and similar immune checkpoints are often overexpressed on human tumors. Thus, dual targeting both innate and adaptive immune checkpoints would likely maximize anti-tumor therapeutic effect and elicit more durable responses...
November 28, 2017: MAbs
https://www.readbyqxmd.com/read/29181191/anti-pd-1-anti-pd-l1-immunotherapy-versus-docetaxel-for-previously-treated-advanced-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis-of-randomised-clinical-trials
#8
Allan Ramos-Esquivel, Alicia van der Laat, Raquel Rojas-Vigott, Melissa Juárez, Luis Corrales-Rodríguez
Background: To compare the efficacy and toxicity of anti-programmed cell death receptor 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) versus docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). Materials and methods: Phase III randomised clinical trials (RCTs) were identified after systematic review of databases and conference proceedings. A random-effect model was used to determine the pooled HR for overall survival (OS), progression-free survival (PFS) and duration of response...
2017: ESMO Open
https://www.readbyqxmd.com/read/29175116/current-and-emergent-therapy-options-for-advanced-squamous-cell-lung-cancer
#9
REVIEW
Mark A Socinski, Coleman Obasaju, David Gandara, Fred R Hirsch, Philip Bonomi, Paul A Bunn, Edward S Kim, Corey J Langer, Ronald B Natale, Silvia Novello, Luis Paz-Ares, Maurice Pérol, Martin Reck, Suresh S Ramalingam, Craig H Reynolds, David R Spigel, Heather Wakelee, Nick Thatcher
Squamous-cell lung cancer (SqCLC) is a distinct histologic subtype of non-small-cell lung cancer (NSCLC) that is challenging to treat due to specific clinicopathologic characteristics, which include older age, advanced disease at diagnosis, co-morbid diseases, and the central location of tumors. These characteristics have a bearing on treatment outcomes in advanced SqCLC, resulting in a median survival approximately 30% shorter than for patients with other NSCLC subtypes. In the context of the specific features of SqCLC, we review challenges of treating SqCLC and the current guideline-recommended treatments for advanced (metastatic) SqCLC in different patient subpopulations...
November 23, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29163822/structural-basis-of-the-therapeutic-anti-pd-l1-antibody-atezolizumab
#10
Fei Zhang, Xiaoqiang Qi, Xiaoxiao Wang, Diyang Wei, Jiawei Wu, Lingling Feng, Haiyan Cai, Yugang Wang, Naiyan Zeng, Ting Xu, Aiwu Zhou, Ying Zheng
Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#11
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29135284/atezolizumab-in-urothelial-bladder-carcinoma
#12
Zineb Hamilou, Pernelle Lavaud, Yohann Loriot
Metastatic bladder cancer is an aggressive malignancy with a poor prognosis when presenting with advanced stage. Cisplatin-based therapy has been the mainstay of first-line treatment but therapy in second-line setting has been an unmet medical need for decades. Moreover, many patients are unable to receive cisplatin-based therapy. Recently, immune-checkpoint inhibitors transformed the management and prognosis of many malignancies and will certainly redefine the standard of care for bladder cancer. Atezolizumab, an antiprogrammed cell death ligand-1 antibody, was the first immune-checkpoint inhibitor to be approved by the US FDA in May 2016 for patients with urothelial carcinoma...
November 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/29120911/immunotherapy-for-kidney-cancer-status-quo-and-the-future
#13
Jens Bedke, Viktoria Stühler, Arnulf Stenzl, Bernhard Brehmer
PURPOSE OF REVIEW: The treatment landscape in advanced and metastatic renal cell carcinoma (RCC) is moving from the inhibition of tyrosine kinases (TKI) and the mammalian target of rapamycin (mTOR) inhibitors to specific immunooncology agents like immune checkpoint inhibitors (ICI). The review focus on the recent immunooncology developments and available trial results within the last 12 months. RECENT FINDINGS: ICI as monotherapy (nivolumab) or immunooncology and immunooncology combinations (nivolumab and ipilimumab) demonstrated positive results on prolonged overall survival in phase III trials...
November 7, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/29115057/smoking-and-egfr-status-may-predict-outcomes-of-advanced-nsclc-treated-with-pd-l-1-inhibitors-beyond-first-line-a-meta-analysis
#14
Omar Abdel-Rahman
OBJECTIVES: To assess the potential clinical and biological predictive markers of survival in pretreated advanced NSCLC patients treated with the three PD-(L)1 inhibitors (nivolumab, pembrolizumab, atezolizumab). Data source/ study selection: PubMed database has been searched. The review author extracted relevant information on participant characteristics and study outcomes for this review and assessed risk of bias of the included trials. Data analysis was conducted through RevMan v.5...
November 8, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/29104763/cardiotoxicity-of-immune-checkpoint-inhibitors
#15
REVIEW
Gilda Varricchi, Maria Rosaria Galdiero, Giancarlo Marone, Gjada Criscuolo, Maria Triassi, Domenico Bonaduce, Gianni Marone, Carlo Gabriele Tocchetti
Cardiac toxicity after conventional antineoplastic drugs (eg, anthracyclines) has historically been a relevant issue. In addition, targeted therapies and biological molecules can also induce cardiotoxicity. Immune checkpoint inhibitors are a novel class of anticancer drugs, distinct from targeted or tumour type-specific therapies. Cancer immunotherapy with immune checkpoint blockers (ie, monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its ligand (PD-L1)) has revolutionised the management of a wide variety of malignancies endowed with poor prognosis...
2017: ESMO Open
https://www.readbyqxmd.com/read/29093678/immune-related-adverse-events-associated-with-anti-pd-1-pd-l1-treatment-for-malignancies-a-meta-analysis
#16
Peng-Fei Wang, Yang Chen, Si-Ying Song, Ting-Jian Wang, Wen-Jun Ji, Shou-Wei Li, Ning Liu, Chang-Xiang Yan
Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence. Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29084031/companion-and-complementary-diagnostics-focus-on-pd-l1-expression-assays-for-pd-1-pd-l1-checkpoint-inhibitors-in-nsclc
#17
Maria Hersom, Jan Trøst Jørgensen
Over the last couple of decades, molecular diagnostics have played an increasing role in drug development. Especially within oncology, more and more drugs are being developed together with a predictive biomarker assay using the drug-diagnostic co-development model. Not only do these assays support the development process but also the use of the drugs after regulatory approval as an important treatment decision tool. When these predictive biomarker assays are linked to a specific drug, they are called companion diagnostics...
October 27, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29082855/comparative-efficacy-and-safety-of-second-line-treatments-for-advanced-non-small-cell-lung-cancer-with-wild-type-or-unknown-status-for-epidermal-growth-factor-receptor-a-systematic-review-and-network-meta-analysis
#18
Perrine Créquit, Anna Chaimani, Amélie Yavchitz, Nassima Attiche, Jacques Cadranel, Ludovic Trinquart, Philippe Ravaud
BACKGROUND: Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis...
October 30, 2017: BMC Medicine
https://www.readbyqxmd.com/read/29080213/looking-for-the-best-immune-checkpoint-inhibitor-in-pre-treated-nsclc-patients-an-indirect-comparison-between-nivolumab-pembrolizumab-and-atezolizumab
#19
Francesco Passiglia, Antonio Galvano, Sergio Rizzo, Lorena Incorvaia, Angela Listì, Viviana Bazan, Antonio Russo
Immune-checkpoint inhibitors represent the new standard of care in patients with advanced NSCLC who progressed after first-line treatment. This work aim to assess any difference in both efficacy and safety profiles among Nivolumab, Pembrolizumab and Atezolizumab in pre-treated NSCLC patients. Randomized clinical trials comparing immune-checkpoint inhibitor versus docetaxel in pre-treated patients with advanced NSCLC were included and direct comparison meta-analysis of selected trials have been performed. Subsequently the summary estimates of Nivolumab, Pembrolizumab and Atezolizumab emerging from the direct meta-analysis were selected to provide the pooled estimates of hazard ratio (HR) and relative risk (RR) for the indirect comparisons among these agents...
October 28, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29079131/update-of-systemic-immunotherapy-for-advanced-urothelial-carcinoma
#20
REVIEW
Benjamin A Gartrell, Tianfang He, Janaki Sharma, Guru Sonpavde
PURPOSE: Until recently, therapeutic options for metastatic urothelial carcinoma (UC) were limited to cytotoxic chemotherapy. Cisplatin-based combination chemotherapy has proven benefit in the perioperative settings for muscle-invasive disease and for metastatic disease. A large proportion of patients is cisplatin-ineligible and limited to less effective chemotherapeutic options. However, treatment options have recently expanded with the development of systemic immunotherapy with checkpoint inhibitors (CPIs)...
October 24, 2017: Urologic Oncology
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