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Checkpoint inhibitors oncology

Bruno L Ferreyro, Laveena Munshi
PURPOSE OF REVIEW: A wide spectrum of heterogeneous conditions can render a patient immunocompromised. Recent years have seen an increase in the number of immunocompromised patients given the earlier detection of conditions that require immunosuppressive therapies, changes in immunosuppressive regimens leading to increased survival or novel therapeutic advancements in oncologic care. Acute respiratory failure (ARF) is the leading cause of critical illness and mortality in this population...
December 3, 2018: Current Opinion in Critical Care
Junaid Raja, Johannes M Ludwig, Scott N Gettinger, Kurt A Schalper, Hyun S Kim
BACKGROUND: Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques...
December 4, 2018: Journal for Immunotherapy of Cancer
Bárbara Meléndez, Claude Van Campenhout, Sandrine Rorive, Myriam Remmelink, Isabelle Salmon, Nicky D'Haene
Immunotherapies based on immune checkpoint inhibitors are emerging as an innovative treatment for different types of advanced cancers. While the utility of immune checkpoint inhibitors has been clearly demonstrated, the response rate is highly variable across individuals. Due to the cost and toxicity of these immunotherapies, a critical challenge in this field is the identification of predictive biomarkers to discriminate which patients may respond to immunotherapy. Recently, a high tumor mutational burden (TMB) has been identified as a genetic signature that is associated with a favorable outcome for immune checkpoint inhibitor therapy...
December 2018: Translational Lung Cancer Research
Ruchi Chaudhary, Luca Quagliata, Jermann Philip Martin, Ilaria Alborelli, Dinesh Cyanam, Vinay Mittal, Warren Tom, Janice Au-Young, Seth Sadis, Fiona Hyland
Background: Tumor mutational burden (TMB) is an increasingly important biomarker for immune checkpoint inhibitors. Recent publications have described strong association between high TMB and objective response to mono- and combination immunotherapies in several cancer types. Existing methods to estimate TMB require large amount of input DNA, which may not always be available. Methods: In this study, we develop a method to estimate TMB using the Oncomine Tumor Mutation Load (TML) Assay with 20 ng of DNA, and we characterize the performance of this method on various formalin-fixed, paraffin-embedded (FFPE) research samples of several cancer types...
December 2018: Translational Lung Cancer Research
Ignacio Morales-Orue, Rodolfo Chicas-Sett, Pedro C Lara
Over the last decade, immunotherapy has emerged as a hopeful alternative in cancer therapy. Different drugs are used to stimulate the immune system and block negative immune regulatory pathways, known as "immune checkpoint inhibitors (ICI)". Although clinical studies have reported efficacy and safety with the use of ICI, only a small group of patients have obtained a clinical benefit. Because of this, immunomodulation based on immunogenic cell death produced by radiotherapy (RT) has been well positioned as an alternative to increase the clinical effect on the primary neoplasm, but also in distant tumours, a phenomenon known as the "abscopal effect"...
January 2019: Reports of Practical Oncology and Radiotherapy
Di Maria Jiang, Srikala S Sridhar
BACKGROUND: Metastatic urothelial cancer (UC) is a lethal disease. Until 2016, cytotoxic chemotherapy with substantial toxicity was the only therapeutic option. In the first-line metastatic setting, cisplatin-based combination chemotherapy remains the standard of care. For cisplatin-ineligible patients, carboplatin-based regimens that are less efficacious are often substituted. In platinum-refractory patients, taxanes and vinflunine are the most commonly used. Recently, treatment options have largely expanded with the development of the immune checkpoint inhibitors (ICIs)...
November 2018: Asia-Pacific Journal of Clinical Oncology
Mathieu Césaire, Juliette Thariat, Serge M Candéias, Dinu Stefan, Yannick Saintigny, François Chevalier
Immunotherapy has revolutionized the practice of oncology, improving survival in certain groups of patients with cancer. Immunotherapy can synergize with radiation therapy, increase locoregional control, and have abscopal effects. Combining it with other treatments, such as targeted therapies, is a promising means of improving the efficacy of immunotherapy. Because the value of immunotherapy is amplified with the expression of tumor antigens, coupling poly(ADP-ribose) polymerase (PARP) inhibitors and immunotherapy might be a promising treatment for cancer...
November 28, 2018: International Journal of Molecular Sciences
Luca Falzone, Salvatore Salomone, Massimo Libra
The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the first modern therapeutic approach in medical oncology...
2018: Frontiers in Pharmacology
Katherine Saunders, Mary S Mably, Sara S Shull, Heather Jones, Ticiana A Leal, Jason J Bergsbaken
Cancer treatment costs in the United States are rising. Evidence suggests that increased costs do not always correlate with improved outcomes. Several organizations have developed tools and frameworks to assess cancer treatment value; however, many centers have reported difficulty in implementing these tools and effectively incorporating value-based decision making into clinical practice. After evaluating existing frameworks, the Carbone Cancer Center at UW Health set out to create a value-based tool that could be used to inform the decisions of clinicians and patients...
November 27, 2018: Journal of Oncology Pharmacy Practice
Julie M Collins, James L Gulley
Although immunotherapies have been employed for many decades, immune checkpoint inhibitors have only recently entered the oncologic landscape. Avelumab is a fully human monoclonal antibody that blocks the interaction between PD-L1 on tumor cells and PD-1 on T cells, thereby inhibiting immunosuppression in the tumor microenvironment and reducing tumor growth. Most early clinical trials of avelumab as monotherapy and in combination regimens were part of the international JAVELIN clinical trial program, which included more than 7000 patients in more than 30 trials with at least 15 tumor types...
November 27, 2018: Human Vaccines & Immunotherapeutics
Tomer Cooks, Sofia Dp Theodorou, Eleni Paparouna, Sophia V Rizou, Vassilios Myrianthopoulos, Vassilis G Gorgoulis, Ioannis S Pateras
In the era of precision medicine immunohistochemistry (IHC) and immunocytochemistry (ICC) share some of the highlights in personalized treatment. Survival data obtained from clinical trials shape the cut-offs and IHC scoring that serve as recommendations for patient selection both for targeted and conventional therapies. Assessment of Estrogen and Progesterone Receptors along with HER2 status has been among the first approved immunostaining assays revolutionizing breast cancer treatment. Similarly, ALK positivity predicts the efficacy of ALK inhibitors in patients with non-small cell lung cancer (NSCLC)...
November 27, 2018: Histology and Histopathology
R M Ruggeri, A Campennì, G Giuffrida, P Trimboli, L Giovanella, F Trimarchi, S Cannavò
Immune checkpoint inhibitors (ICIs) are novel anticancer agents, recently introduced with the aim of boosting the immune response against tumors. ICIs are monoclonal autoantibodies that specifically target inhibitory receptors on T cells: cytotoxic T lymphocyte antigen 4 (CTLA4), programmed death 1 (PD-1) and its ligand (PD-1L). ICIs also generate peculiar dysimmune toxicities, called immune-related adverse events (irAEs), that can potentially affect any tissue, and some may be life-threatening if not promptly recognized...
November 23, 2018: Journal of Endocrinological Investigation
Lara Sánchez-Barroso, Maria Apellaniz-Ruiz, Gerardo Gutiérrez-Gutiérrez, María Santos, Juan M Roldán-Romero, Maria Curras, Laura Remacha, Bruna Calsina, Isabel Calvo, María Sereno, María Merino, Jesús García-Donas, Beatriz Castelo, Eva Guerra, Rocio Letón, Cristina Montero-Conde, Alberto Cascón, Lucía Inglada-Pérez, Mercedes Robledo, Cristina Rodríguez-Antona
BACKGROUND: Peripheral neuropathy is the dose-limiting toxicity of many oncology drugs, including paclitaxel. There is large interindividual variability in the neuropathy, and several risk factors have been proposed; however, many have not been replicated. Here we present a comprehensive study aimed at identifying treatment and physiopathology-related paclitaxel-induced neuropathy risk factors in a large cohort of well-characterized patients. PATIENTS AND METHODS: Analyses included 503 patients with breast or ovarian cancer who received paclitaxel treatment...
November 23, 2018: Oncologist
Vivek Verma, Tanja Sprave, Waqar Haque, Charles B Simone, Joe Y Chang, James W Welsh, Charles R Thomas
BACKGROUND: Escalating healthcare costs are necessitating the practice of value-based oncology. It is crucial to critically evaluate the economic impact of influential but expensive therapies such as immune checkpoint inhibitors (ICIs). To date, no systematic assessment of the cost-effectiveness (CE) of ICIs has been performed. METHODS: PRISMA-guided systematic searches of the PubMed database were conducted. Studies of head/neck (n = 3), lung (n = 5), genitourinary (n = 4), and melanoma (n = 8) malignancies treated with ICIs were evaluated...
November 23, 2018: Journal for Immunotherapy of Cancer
G Myers
Immune checkpoint inhibitors (icis) such as inhibitors of ctla-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (iraes) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality. Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities...
October 2018: Current Oncology
Gabriel Gazzé
The incidence of metastatic melanoma has been increasing dramatically over the last decades. Yet, there have been many new innovative therapies, such as targeted therapies and checkpoint inhibitors, which have made progress in survival for these patients. The oncology pharmacist is part of the healthcare team and can help in optimizing these newer therapies. There will be discussion about combination therapies, the oncology pharmacist's role, and issues at the core of his interest, such as drug interactions and complementary and alternative therapies...
June 2018: Melanoma Management
Gilberto Filaci, Daniela Fenoglio, Lucia Taramasso, Francesco Indiveri, Antonio Di Biagio
The pathogenesis of HIV immunodeficiency is mainly dependent on the cytopatic effects exerted by the virus against infected CD4+ T cells. However, CD4+ T cell loss cannot be the only pathogenic factor since severe opportunistic infections may develop in HIV infected patients with normal CD4+ T cell counts and since the recent START study indicated that absolute CD4+ T cell counts are not predictive for AIDS and non-AIDS events. Recently our group demonstrated that CD8+CD28-CD127lowCD39+ regulatory T lymphocytes, previously found highly concentrated within tumor microenvironment, circulate with elevated frequency in the peripheral blood of HIV infected patients...
2018: Frontiers in Immunology
Colleen B Warren
BACKGROUND: By using the body's own protective system to fight cancer, immunotherapy is not only effective but also is associated with fewer side effects than chemotherapy. OBJECTIVES: This article provides an overview of four types of immunotherapy (monoclonal antibodies, chimeric antigen receptors, immune checkpoint inhibitors, and cancer vaccines) and discusses the critical role assumed by nurses in the care of patients receiving immunotherapy. METHODS: A review of the literature was undertaken to identify, describe, and compare the types of immunotherapy used and studied for use in pediatric oncology...
December 1, 2018: Clinical Journal of Oncology Nursing
Volker Endris, Ivo Buchhalter, Michael Allgäuer, Eugen Rempel, Amelie Lier, Anna-Lena Volckmar, Martina Kirchner, Moritz von Winterfeld, Jonas Leichsenring, Olaf Neumann, Roland Penzel, Wilko Weichert, Hanno Glimm, Stefan Fröhling, Hauke Winter, Felix Herth, Michael Thomas, Peter Schirmacher, Jan Budczies, Albrecht Stenzinger
Assessment of Tumor Mutational Burden (TMB) for response stratification of cancer patients treated with immune checkpoint inhibitors is emerging as a new biomarker. Commonly defined as the total number of exonic somatic mutations, TMB approximates the amount of neoantigens that potentially are recognized by the immune system. While whole exome sequencing (WES) is an unbiased approach to quantify TMB, implementation in diagnostics is hampered by tissue availability as well as time and cost constrains. Conversely, panel-based targeted sequencing is nowadays widely used in routine molecular diagnostics, but only very limited data are available on its performance for TMB estimation...
November 17, 2018: International Journal of Cancer. Journal International du Cancer
Cong Ava Fan, Jocelyn Reader, Dana M Roque
The rise of immunotherapy is the greatest advance in oncology to occur over the last several years, but applications in gynecologic malignancies lag behind other tumors. The term "immunotherapy" envelops monoclonal antibodies as receptor mediators, including immune checkpoint inhibitors (ICPI), cancer vaccines, and adoptive immunotherapies alone or in combination with other therapeutic approaches. The purpose of this review is to summarize the status of immunotherapy trials in ovarian cancer and to specifically highlight data published in the last 1-2 years...
November 14, 2018: Current Treatment Options in Oncology
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