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Checkpoint inhibitors oncology

Yada Kanjanapan, Daphne Day, Lisa Wang, Hamad Al-Sawaihey, Engy Abbas, Amirali Namini, Lillian L Siu, Aaron Hansen, Albiruni Abdul Razak, Anna Spreafico, Natasha Leighl, Anthony M Joshua, Marcus O Butler, David Hogg, Mary Anne Chappell, Ludmilla Soultani, Kayla Chow, Samantha Boujos, Philippe L Bedard
BACKGROUND: A subset of patients treated with immune checkpoint inhibitors experience an accelerated tumor growth rate (TGR) in comparison with pretreatment kinetics; this is known as hyperprogression. This study assessed the relation between hyperprogressive disease (HPD) and treatment-related toxicity and clinical factors. METHODS: This study reviewed patients with solid tumors who were enrolled in early-phase immunotherapy trials at Princess Margaret Cancer Centre between August 2012 and September 2016 and had computed tomography scans in the pre-immunotherapy (reference) and on-immunotherapy (experimental) periods...
February 15, 2019: Cancer
Hisataka Kobayashi
Near infrared photoimmunotherapy(NIR-PIT)is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IRDye700DX(IR700), to a monoclonal antibody(mAb)targeting cell-surface molecules. NIR-PIT targetingEGFR usingthe cetuximab-IR700 conjugate is now in transition to fast-track global Phase Ⅲ clinical trial in late-stage head and neck squamous cell cancer patients. When exposed to NIR light, the conjugate induces a highlyselective necrotic/immunogenic cell death(ICD)only in target-positive, mAb-IR700-bound cancer cells...
January 2019: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Timothy M Markman, Maurie Markman
Traditional chemotherapeutic agents and newer targeted therapies for cancer have the potential to cause cardiovascular toxicities. These toxicities can result in arrhythmias, heart failure, vascular toxicity, and even death. It is important for oncologists and cardiologists to understand the basic diagnostic and management strategies to employ when these toxicities occur. While anti-neoplastic therapy occasionally must be discontinued in this setting, it can often be maintained with caution and careful monitoring...
2019: F1000Research
Margaret Ottaviano, Sabino De Placido, Paolo Antonio Ascierto
AbstractSeveral researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient's immune system in the way of restore or induce a response to cancer. As a consequence, "cancer immunotherapy" is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of anti-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the treatment of a variety of malignancies...
February 12, 2019: Virchows Archiv: An International Journal of Pathology
Rui Chen, Xiaoming Hou, Liping Yang, Da Zhao
BACKGROUND: Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, and most clinically curable patients are diagnosed with locally advanced disease. Although the efficacy of standard platinum-based chemotherapy doublets is relatively limited. The effect of immune checkpoint inhibitors (ICIs) remains controversial, and its role in the first-line treatment of advanced NSCLC is obscure. Thus, we carried out a systematic review and meta-analysis to compare the efficacy and safety of ICIs for advanced NSCLC...
February 7, 2019: Thoracic Cancer
Yumi Yokoyama, Erin D Lew, Ruth Seelige, Elizabeth A Tindall, Colin Walsh, Patrick C Fagan, Jack Y Lee, Robin Nevarez, Joanne Oh, Kathleen D Tucker, Marissa Chen, Amy Diliberto, Heather Vaaler, Kristen M Smith, Amanda Albert, Gary Li, Jack D Bui
Expression of the TAM (TYRO3, AXL, MER) family of receptor tyrosine kinases (RTK) has been associated with cancer progression, metastasis, and drug resistance. In immune cells, TAM RTKs can dampen inflammation in favor of homeostatic wound healing responses, thus potentially contributing to the evasion of cancer cells from immune surveillance. Here we characterize the small molecule RXDX-106 as a selective and potent pan-TAM RTK inhibitor with slow dissociation kinetics and significant anti-tumor activity in multiple syngeneic tumor models...
February 5, 2019: Cancer Research
Emily A Lemke, Amishi Yogesh Shah
Bladder cancer is the sixth most common cancer in the United States; therefore, the majority of clinicians working in the oncology setting will care for this patient population. Unfortunately, treatment plans, especially in the advanced setting, lack consistency. This, along with the advanced age and comorbidities of most bladder cancer patients, can provide challenges for clinicians when developing treatment plans. In the past 2 years, new drug approvals, specifically those for immune checkpoint inhibitors, have changed the treatment landscape for bladder cancer for the first time since the 1980s...
May 2018: Journal of the Advanced Practitioner in Oncology
Oliver J Müller, Martina E Spehlmann, Norbert Frey
Immune checkpoint inhibitors (ICIs) have started revolutionizing the treatment of numerous advanced oncological diseases by restoring immune resistance against cancer cells. ICI-associated cardiac adverse effects are rare, but severe. About 50% of cardiac complications comprise myocarditis with variable clinical presentation and a high rate of fatality. The pathomechanism is incompletely understood and may involve preexisting autoimmunity such as autoantibodies or common epitopes shared by cardiomyocytes and tumor cells...
December 2018: Journal of Thoracic Disease
Niels Reinmuth, Michael Bitzer, Barbara Deschler-Baier, Jürgen R Fischer, Jonas Kuon, Jan Leipe, Justyna Rawluk, Christian Schulz, Claus Peter Heußel, Michael Schultheiß
The immune oncological treatment approach uses immune checkpoint inhibitors to prevent tumor cells from shutting down the immune system, and thus from escaping immune response. Following the clinical success of immune checkpoint inhibitors, the number of approved immune oncological therapies continues to increase. Response rates and overall survival with anti-PD-1/PD-L1 and CTLA-4 blockade could be further improved by combining both treatment approaches. However, checkpoint inhibition is associated with a unique spectrum of side effects termed immune-related adverse events...
January 30, 2019: Deutsche Medizinische Wochenschrift
Eugene Muchnik, Kah Poh Loh, Myla Strawderman, Allison Magnuson, Supriya G Mohile, Vered Estrah, Ronald J Maggiore
OBJECTIVE: To evaluate the efficacy and toxicity of immune checkpoint inhibitors (ICIs) in older patients with advanced non-small cell lung cancer (NSCLC) seen in routine clinical practice. DESIGN: Retrospective study. SETTING: Single academic institution and its affiliated centers. PARTICIPANTS: Patients 70 years or older with advanced-stage NSCLC seen between April 1, 2015, and April 1, 2017, and treated with ICIs...
January 30, 2019: Journal of the American Geriatrics Society
Brett Hamilton, Kay Xu, Florian Honeyball, Bavanthi Balakrishnar, Rob Zielinski
BACKGROUND: The introduction of the CTLA-4 and PD-1 immune checkpoint inhibitors and their subsequent listing on the PBS for use in metastatic melanomas, renal cell carcinomas and non-small cell lung cancers has resulted in routine use of these agents in oncology practices, including in regional areas. Although immunotherapeutic agents generally have a favourable toxicity profile compared to chemotherapy, they can provoke immune-related adverse effects (irAEs) caused by an unregulated and hyperstimulated immune response...
January 28, 2019: Internal Medicine Journal
Do Young Kim
Since the approval of sorafenib for patients with advanced hepatocellular carcinoma (HCC) in 2007, many drugs have failed in the first and second-line setting. Fortunately, during the recent 2 years, between 2017 and 2018, four drugs (regorafenib, lenvatinib, cabozantinib, and ramucirumab) were found to be effective and tolerable for patients with HCC as the first- or second-line therapy. Regorafenib, a multi-kinase inhibitor, has a similar structure to sorafenib, and was shown to improve the survival of patients who progressed after sorafenib treatment compared to the placebo control...
January 25, 2019: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
Tiffany Seto, Danny Sam, Minggui Pan
Immune checkpoint inhibitors (ICPis) have revolutionized cancer therapy with broad activities against a wide range of malignancies. However, in many malignancies their efficacy remains limited due to the primary resistance. Furthermore, a high percentage of patients develop progression due to the secondary resistance even after obtaining a response or achieving a stable disease. In this review, we will discuss the mechanisms that underlie the primary and secondary resistance to ICPis in cancer immunotherapy and provide an overview to impart a broad understanding of the critical issues that are encountered in clinical oncology practice...
January 22, 2019: Medical Sciences: Open Access Journal
Jacob S Young, Fara Dayani, Ramin A Morshed, Hideho Okada, Manish K Aghi
The current standard of care for patients with high grade gliomas includes surgical resection, chemotherapy, and radiation; but even still the majority of patients experience disease progression and succumb to their illness within a few years of diagnosis. Immunotherapy, which stimulates an anti-tumor immune response, has been revolutionary in the treatment of some hematological and solid malignancies, generating substantial excitement for its potential for patients with glioblastoma. The most commonly used immunotherapies include dendritic cell and peptide vaccines, checkpoint inhibitors, and adoptive T cell therapy...
January 21, 2019: World Neurosurgery
Matthias Totzeck, Martin Schuler, Martin Stuschke, Gerd Heusch, Tienush Rassaf
Current therapy of advanced cancers is based on several modalities including radiotherapy, cytotoxic chemotherapy, molecularly targeted inhibitors and antibodies targeting immune checkpoints. All of those these modalities can negatively impact the cardiovascular system, and there is considerable experience in relation to radiotherapy and chemotherapy. In contrast, the knowledge base on cardiovascular toxicities of novel agents targeting signal transduction pathways and immune regulation is quite limited. In particular, potential late effects are of concern as cardiovascular pathology can negatively impact quality of life and prognosis in cancer survivors, particularly when additional cardiovascular risk factors are present...
January 11, 2019: International Journal of Cardiology
Brandon A Dyer, Dmitriy Zamarin, Ramez N Eskandar, Jyoti M Mayadev
Despite combined therapeutic approaches, there is an unmet clinical need to identify effective strategies for improved patient outcomes in treating locally advanced and metastatic cervical cancer (CC). Immunotherapy is emerging as a novel therapeutic approach in this disease for which the causative agent, human papillomavirus (HPV), has dynamic, complex immunomodulatory effects. This review explores the biologic rational of immuno-oncology in the treatment of CC and discusses the initial clinical efficacy, ongoing clinical trials, and rationale for combined multimodal treatment approaches for locally advanced and recurrent/metastatic CC...
January 2019: Journal of the National Comprehensive Cancer Network: JNCCN
Benjamin P Levy, Giuseppe Giaccone, Benjamin Besse, Enriqueta Felip, Marina Chiara Garassino, Manuel Domine Gomez, Pilar Garrido, Bilal Piperdi, Santiago Ponce-Aix, Daniel Menezes, Kyle J MacBeth, Alberto Risueño, Ruta Slepetis, Xiaoling Wu, Abderrahim Fandi, Luis Paz-Ares
INTRODUCTION: Preclinical and early clinical studies suggest that combining epigenetic agents with checkpoint inhibitors can potentially improve outcomes in patients with previously treated advanced non-small cell lung cancer (NSCLC). This phase 2 trial examined second-line pembrolizumab + CC-486 (oral azacitidine) in patients with advanced NSCLC. METHODS: Patients with one prior line of platinum-containing therapy were randomised in a ratio of 1:1 to CC-486 or placebo, on days 1-14, in combination with pembrolizumab on day 1 of a 21-day cycle...
January 14, 2019: European Journal of Cancer
Jenessa Lee, Anastasia Graham, Amy Sion
Immune checkpoint inhibitors are being commonly used as anticancer therapies to treat malignancies. Immune checkpoint inhibitors have been associated with numerous immune-related adverse events (irAEs). IrAEs are well documented; however, rheumatic irAEs are infrequently reported in published literature. The objective of this single-center retrospective chart review study was to evaluate the incidence of arthralgias with immune checkpoint inhibitor therapy as well as the management of these immune-related events...
January 16, 2019: Journal of Oncology Pharmacy Practice
Lukas Käsmann, Chukwuka Eze, Maurice Dantes, Olarn Roengvoraphoj, Maximilian Niyazi, Claus Belka, Farkhad Manapov
Combinations of immune checkpoint inhibitors (ICIs) with radiotherapy and/or chemoradiotherapy are currently under investigation in many cancer types and clinical settings. In this survey, we solicited members of the German Radiation Oncology Society and young DEGRO (working group of DEGRO e.V.) to review the current status of research in this field and underline critical issues such as oncological benefit, treatment toxicity and obstacles in clinical research. The responses represent 14 different departments of radiation oncology at German university hospitals...
January 12, 2019: European Journal of Cancer
Marie Dilly-Feldis, Nathalie Aladjidi, John K Refait, Marie Parrens, Stéphane Ducassou, Anne Rullier
BACKGROUND: Although a prognosis of recurrent or refractory childhood Hodgkin lymphoma (HL) is associated with poor outcomes despite intensive therapy, the immune checkpoint inhibitors PD-1/PD-L1 appear to be therapeutic alternatives for advanced adult cases. However, these pharmacotherapies are yet to be studied in a pediatric population. PROCEDURE: The present study measured the expression of PD-1/PD-L1 in diagnostic samples of children with classical HL, according to the disease course...
January 13, 2019: Pediatric Blood & Cancer
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