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Alessandro Morabito
The therapeutic scenario of patients with advanced non-small-cell lung cancer (NSCLC) has dramatically changed in recent years, thanks to the improvement in the knowledge of the biology of NSCLC, the discovery of targetable oncogenic drivers, and the availability of new effective drugs also for non oncogenic addicted patients, defined "wild-type" (WT). NSCLC has been the first epithelial neoplasm treated with a targeted first-line therapy in patients harbouring EGFR activating mutations or ALK rearrangements, and new targeted-based agents directed versus other molecular alterations are currently in development...
October 2016: Recenti Progressi in Medicina
Chee Khoon Lee, Johnathan Man, Sally Lord, Matthew Links, Val Gebski, Tony Mok, James Chih-Hsin Yang
INTRODUCTION: We performed a meta-analysis to assess the role of immune-checkpoint inhibitors as second-line therapy in epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC). METHODS: Randomized trials comparing immune-checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation defined subgroups...
October 17, 2016: Journal of Thoracic Oncology
Julie Bonigen, Christine Raynaud-Donzel, José Hureaux, Nora Kramkimel, Astrid Blom, Géraldine Jeudy, Anne-Laure Breton, Thomas Hubiche, Christophe Bedane, Delphine Legoupil, Anne Pham-Ledard, Julie Charles, Maurice Pérol, Emilie Gérard, Patrick Combemale, Daphné Bonnet, Michèle-Léa Sigal, Emmanuel Mahé
Nivolumab (Opdivo(®) ), pembrolizumab (Keytruda(®) ), atezolizumab, and pidilizumabab are anti-PD1 monoclonal antibodies. Nivolumab is licensed in advanced melanoma and second-line therapy of advanced or metastatic non-small cell lung cancer. When activated, the programmed cell death (PD)-1 is implicated in the inhibition of the immune system. Anti-PD1 removes this inhibition and allows the immune system to control tumour cell progression.(1-4) Immune-mediated toxicity of this treatment have been reported, either organ-specific toxicities - i...
October 14, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Xi Chen, Jin Xu, Qingcheng Guo, Lingfei Wang, Yun Yang, Huaizu Guo, Nana Gu, Dapeng Zhang, Weizhu Qian, Sheng Hou, Jing Li, Jianxin Dai, Yajun Guo, Hao Wang
Immunocytokines (antibody-cytokine fusions) have been proved to be a promising class of therapeutic agents for tumors. Anti-PD-L1 antibodies or IL-2 have been used to treat a variety of cancers. Here, in order to remove T cell inhibition and increasing the IL-2 concentration in the tumor microenvironment, we engineered a novel anti-PD-L1 antibody based immunocytokine by fusing hIL-2 to the C-Term of atezolizumab, denoted as BIPI. Our results revealed that BIPI was effective in stimulating T cell activation in vitro and could selectively localize to the tumor...
October 5, 2016: Biochemical and Biophysical Research Communications
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
G Santabarbara, P Maione, A Rossi, G Palazzolo, C Gridelli
INTRODUCTION: Lung cancers remain the principal cause of death cancer-related worldwide with a poor survival rate at five years from diagnosis. In patients with NSCLC harboring specific genetic alterations the anti EGFR TKIs and the ALK TKIs have improved the response rate and the quality of life compared to standard platinum-based chemotherapy. New approaches possibly applicable at the major of patients are needed. AREAS COVERED: The discovery that the immune system plays a fundamental role in the fight against cancer...
September 23, 2016: Expert Review of Clinical Pharmacology
Stephanie A Mullane, Joaquim Bellmunt
PURPOSE OF REVIEW: Immunotherapy in urological cancer has made substantial progress during the last 20 years, but recent advances in immunotherapy have completely transformed the present treatment landscape. In this review, we summarize major clinical achievements of immunotherapy in genitourinary cancers, as well as address potential new directions for these therapies, including new agents, combinations, and biomarkers. RECENT FINDINGS: Recently, nivolumab and atezolizumab have joined sipuleucel-T as Food and Drug Administration-approved therapies in urological malignancies...
November 2016: Current Opinion in Urology
Jeffrey J Wallin, Johanna C Bendell, Roel Funke, Mario Sznol, Konstanty Korski, Suzanne Jones, Genevive Hernandez, James Mier, Xian He, F Stephen Hodi, Mitchell Denker, Vincent Leveque, Marta Cañamero, Galina Babitski, Hartmut Koeppen, James Ziai, Neeraj Sharma, Fabien Gaire, Daniel S Chen, Daniel Waterkamp, Priti S Hegde, David F McDermott
Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC...
August 30, 2016: Nature Communications
Helena Linardou, Helen Gogas
Checkpoint inhibitors have revolutionized the treatment of patients with metastatic melanoma offering improved responses and significant survival benefit. These agents are now approved for the treatment of metastatic melanoma, squamous and non-squamous non-small cell lung cancer (NSCLC) and kidney cancer, while they are now being investigated in a range of other malignancies. In addition, another anti-PD-L1 monoclonal antibody (atezolizumab) was recently approved for urothelial cancer. Ipilimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody and the anti-PD-1 agents nivolumab and pembrolizumab have followed large clinical development programs, therefore, information regarding their safety and toxicity profile is readily available...
July 2016: Annals of Translational Medicine
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
Dennis J Cada, Terri L Levien, Danial E Baker
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers...
July 2016: Hospital Pharmacy
Paul C Barnfield, Peter M Ellis
Platinum-based doublet chemotherapy with or without bevacizumab is the standard of care for the initial management of advanced and metastatic non-small cell lung cancer (NSCLC) without a targetable molecular abnormality. However, the majority of patients with NSCLC will ultimately develop resistance to initial platinum-based chemotherapy, and many remain candidates for subsequent lines of therapy. Randomised trials over the past 10-15 years have established pemetrexed (non-squamous histology), docetaxel, erlotinib and gefitinib as approved second-line agents in NSCLC without targetable driver mutations or rearrangements...
September 2016: Drugs
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
Alain P Algazi, Katy K Tsai, Alexander N Shoushtari, Rodrigo R Munhoz, Zeynep Eroglu, Josep M Piulats, Patrick A Ott, Douglas B Johnson, Jimmy Hwang, Adil I Daud, Jeffrey A Sosman, Richard D Carvajal, Bartosz Chmielowski, Michael A Postow, Jeffrey S Weber, Ryan J Sullivan
BACKGROUND: Antibodies inhibiting the programmed death receptor 1 (PD-1) have demonstrated significant activity in the treatment of advanced cutaneous melanoma. The efficacy and safety of PD-1 blockade in patients with uveal melanoma has not been well characterized. METHODS: Fifty-eight patients with stage IV uveal melanoma received PD-1 or PD-1 ligand (PD-L1) antibodies between 2009 and 2015 at 9 academic centers. Patients who were evaluable for response were eligible for the analysis...
August 17, 2016: Cancer
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
Wojciech G Lesniak, Samit Chatterjee, Matthew Gabrielson, Ala Lisok, Bryan Wharram, Martin G Pomper, Sridhar Nimmagadda
The programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pair is a major immune checkpoint pathway exploited by cancer cells to develop and maintain immune tolerance. With recent approvals of anti-PD-1 and anti-PD-L1 therapeutic antibodies, there is an urgent need for noninvasive detection methods to quantify dynamic PD-L1 expression in tumors and to evaluate the tumor response to immune modulation therapies. To address this need, we assessed [(64)Cu]atezolizumab for the detection of PD-L1 expression in tumors...
September 21, 2016: Bioconjugate Chemistry
Anshu Giri, Simrit S Walia, Ajeet Gajra
INTRODUCTION: Non-Small Cell Lung Cancer (NSCLC) is an aggressive malignancy with poor overall survival that accounts for up to 85% of lung cancer diagnoses. The use of immunotherapy in the form of checkpoint inhibition, to enhance the immune system's ability to attack malignant cells, has been a promising addition to treatment options in advanced NSCLC. RESULTS: Such therapeutic agents aimed at the Programmed Death 1 (PD-1) receptor or Programmed Death Ligand 1 (PD-L1) have revealed promising results against many types of cancer including NSCLC...
July 24, 2016: Reviews on Recent Clinical Trials
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