المؤلفون: Conroy, Michael, Naidoo, Jarushka

المصدر: Nature Communications
Nature Communications, Vol 13, Iss 1, Pp 1-4 (2022)

مصطلحات موضوعية: Clinical Trials as Topic, Multidisciplinary, Adverse effects, Science, animal diseases, Comment, General Physics and Astronomy, chemical and pharmacologic phenomena, Cancer immunotherapy, General Chemistry, biochemical phenomena, metabolism, and nutrition, General Biochemistry, Genetics and Molecular Biology, Prognostic markers, Disease Models, Animal, Neoplasms, bacteria, Tumour immunology, Animals, Humans, Immunotherapy, Immune Checkpoint Inhibitors

الوصف: The benefit from immune checkpoint inhibitors is tempered by immunologic toxicities, which involve diverse organs, have varying biology, onset time, and severity. Herein, we identify important areas of controversy and open research questions in the field of immune-related toxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a939ab57a622ba627c973f19213252b9Test
https://doi.org/10.1038/s41467-022-27960-2Test

المؤلفون: Fitzpatrick,Orla, Naidoo,Jarushka

المصدر: Lung Cancer: Targets and Therapy.

مصطلحات موضوعية: Targets and Therapy [Lung Cancer]

الوصف: Orla Fitzpatrick,1 Jarushka Naidoo1,2 1Department of Oncology, Beaumont Hospital, RCSI University of Health Sciences, Dublin, Ireland; 2Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, 21231, USACorrespondence: Jarushka NaidooBeaumont Hospital, Beaumont Road, Dublin, 9, Ireland, Tel +353 1 809-3000Email jnaidoo1@jhmi.eduAbstract: Immunocheckpoint inhibitors (ICIs) have altered the treatment landscape of a wide range of malignancies, including non–small cell lung cancer (NSCLC). This class of agents inhibits the interaction between PD1 and PDL1, and was shown to be efficacious in the landmark PACIFIC trial with 1 year of maintenance durvalumab (anti-PDL1 antibody). This trial demonstrated that its use as a consolidation treatment given after definitive chemoradiotherapy improved progression free survival and overall survival compared to standard-of-care treatment. In this review, we discuss both clinical trial and real-world data that have been published since PACIFIC that support the use of durvalumab for stage III unresectable NSCLC. In addition, we highlight specific populations that may require special considerations for the use of durvalumab in this setting, such as oncogene-addicted NSCLC, the toxicity of immunotherapy, and future directions in ICI research in stage III NSCLC.Keywords: lung cancer, immunotherapy, durvalumab

وصف الملف: text/html

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dovemedicalp::6e673d2985a98e330d4419281896c0afTest
https://www.dovepress.com/immunotherapy-for-stage-iii-nsclc-durvalumab-and-beyond-peer-reviewed-fulltext-article-LCTTTest

المؤلفون: Faivre-Finn, Corinne, Vicente, David, Kurata, Takayasu, Planchard, David, Paz-Ares, Luis, Vansteenkiste, Johan F, Spigel, David R, Garassino, Marina C, Reck, Martin, Senan, Suresh, Naidoo, Jarushka, Rimner, Andreas, Wu, Yi-Long, Gray, Jhanelle E, Özgüroğlu, Mustafa, Lee, Ki H, Cho, Byoung C, Kato, Terufumi, de Wit, Maike, Newton, Michael, Wang, Lu, Thiyagarajah, Piruntha, Antonia, Scott J

المساهمون: Radiation Oncology, CCA - Cancer Treatment and quality of life

المصدر: Journal of Thoracic Oncology, 16(5), 860-867. International Association for the Study of Lung Cancer
Faivre-Finn, C, Vicente, D, Kurata, T, Planchard, D, Paz-Ares, L, Vansteenkiste, J F, Spigel, D R, Garassino, M C, Reck, M, Senan, S, Naidoo, J, Rimner, A, Wu, Y-L, Gray, J E, Özgüroğlu, M, Lee, K H, Cho, B C, Kato, T, de Wit, M, Newton, M, Wang, L, Thiyagarajah, P & Antonia, S J 2021, ' Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC—an Update From the PACIFIC Trial : Four-year survival with durvalumab after chemoradiotherapy in Stage III NSCLC-an update from the PACIFIC trial ', Journal of Thoracic Oncology, vol. 16, no. 5, pp. 860-867 . https://doi.org/10.1016/j.jtho.2020.12.015Test

الوصف: Introduction: In the Phase 3, placebo-controlled PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression after concurrent chemoradiotherapy, consolidative durvalumab was associated with significant improvements in the primary end points of overall survival (OS) (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.53–0.87; p = 0.00251; data cutoff, March 22, 2018) and progression-free survival (PFS) (blinded independent central review; Response Evaluation Criteria in Solid Tumors version 1.1) (HR = 0.52; 95% CI: 0.42–65; p < 0.0001; February 13, 2017) with manageable safety. Here, we report updated analyses of OS and PFS, approximately 4 years after the last patient was randomized. Methods: Patients with WHO performance status of 0 or 1 (and any tumor programmed death-ligand 1 status) were randomized (2:1) to intravenous durvalumab (10 mg/kg) or placebo, administered every 2 weeks (≤12 months), stratified by age, sex, and smoking history. OS and PFS were analyzed using a stratified log-rank test in the intent-to-treat population. Medians and 4-year OS and PFS rates were estimated by the Kaplan–Meier method. Results: Overall, 709 of 713 randomized patients received durvalumab (n/N=473/476) or placebo (n/N=236/237). As of March 20, 2020 (median follow-up = 34.2 months; range: 0.2–64.9), updated OS (HR = 0.71; 95% CI: 0.57–0.88) and PFS (HR = 0.55; 95% CI: 0.44–0.67) remained consistent with the primary analyses. The median OS for durvalumab was reached (47.5 mo; placebo, 29.1 months). Estimated 4-year OS rates were 49.6% versus 36.3% for durvalumab versus placebo, and 4-year PFS rates were 35.3% versus 19.5% respectively. Conclusion: These updated exploratory analyses demonstrate durable PFS and sustained OS benefit with durvalumab after chemoradiotherapy. An estimated 49.6% of patients randomized to durvalumab remain alive at 4 years (placebo, 36.3%), and 35.3% remain alive and progression-free (placebo, 19.5%).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::602618f5148c30902a1d333f2d59775eTest
https://research.vumc.nl/en/publications/b0a92c20-2c30-4246-a25a-5eb1259632afTest

المؤلفون: Suresh, Karthik, Naidoo, Jarushka, Lin, Cheng Ting, Danoff, Sonye

مصطلحات موضوعية: Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Special Feature, Humans, Risk Adjustment, Immunotherapy, Pneumonia, Patient Care Management

الوصف: Immune checkpoint inhibitors (ICIs) are newer, immunotherapy-based drugs that have been shown to improve survival in advanced non-small cell lung cancer (NSCLC). Unlike traditional chemotherapeutic agents, ICIs work by boosting the body's natural tumor killing response. However, this unique mechanism of action has also led to the recognition of class-specific side effects. Labeled immune-related adverse events, these toxicities can affect multiple organ systems including the lungs. Immune-mediated lung injury because of ICI use, termed checkpoint inhibitor pneumonitis (CIP), occurs in about 3% to 5% of patients receiving ICIs; however, the real-world incidence of this entity may be higher, especially now that ICIs are being used in nonclinical trial settings. In this review, we briefly introduce the biology of ICIs and the indications for ICI use in NSCLC and then discuss the epidemiology and clinical and radiologic manifestations of CIP. Next, we discuss management strategies for CIP, including the current consensus on management of steroid-refractory CIP. Given the nascent nature of this field, we highlight areas of uncertainty and emerging research questions in the burgeoning field of checkpoint inhibitor pulmonary toxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::5b421881ec6afe53c8bfa3e967b969beTest
https://europepmc.org/articles/PMC6335259Test/

المؤلفون: Jiun-Ruey Hu, Evan J. Lipson, Robert F. Padera, Douglas B. Johnson, Alexander R. Lyon, Jarushka Naidoo, Roberta Florido, Javid Moslehi, Carlo G. Tocchetti, Reza Ardehali

المساهمون: Hu, Jiun-Ruey, Florido, Roberta, Lipson, Evan J, Naidoo, Jarushka, Ardehali, Reza, Tocchetti, Carlo G, Lyon, Alex R, Padera, Robert, Johnson, Douglas B, Moslehi, Javid

مصطلحات موضوعية: Cardiotoxicity, Myocarditis, Physiology, business.industry, Cancer, medicine.disease, Bioinformatics, Myasthenia gravis, Immune system, Physiology (medical), medicine, Arteritis, Cardiology and Cardiovascular Medicine, Vasculitis, business, Myositis

الوصف: Cardiovascular toxicities associated with immune checkpoint inhibitors (ICIs) have been reported in case series but have been underappreciated due to their recent emergence, difficulties in diagnosis and non-specific clinical manifestations. ICIs are antibodies that block negative regulators of the T cell immune response, including cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and PD-1 ligand (PD-L1). While ICIs have introduced a significant mortality benefit in several cancer types, the augmented immune response has led to a range of immune-related toxicities, including cardiovascular toxicity. ICI-associated myocarditis often presents with arrhythmias, may co-exist with myositis and myasthenia gravis, can be severe, and portends a poor prognosis. In addition, pericardial disease, vasculitis, including temporal arteritis, and non-inflammatory heart failure, have been recently described as immune-related toxicities from ICI. This narrative review describes the epidemiology, diagnosis, pathophysiology, and treatment of cardiovascular toxicities of ICI therapy, highlighting recent developments in the field in the past year.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a7b5a12a890d546f0285c658a2d48491Test
http://hdl.handle.net/11588/739138Test