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https://www.readbyqxmd.com/read/28430376/acute-generalized-exanthematous-pustulosis-associated-with-ipilimumab-and-nivolumab
#1
Basile Page, Luca G Borradori, Helmut Beltraminelli, Nikhil Yawalkar, Robert E Hunger
Acute generalized exanthematous pustulosis (AGEP) is a rare potentially severe adverse cutaneous eruption, that is usually induced by a variety of drugs, most commonly anti-bacterial drugs. AGEP is characterized by the acute development of extensive, non-follicular, sterile pustules on an erythematous background accompanied by systemic symptoms such as fever and leucocytosis.¹ The prognosis is usually favourable, but in elderly patients with comorbidities morbidity and mortality are increased.² This article is protected by copyright...
April 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28428947/update-on-programmed-death-1-and-programmed-death-ligand-1-inhibition-in-the-treatment-of-advanced-or-metastatic-non-small-cell-lung-cancer
#2
REVIEW
Marco A J Iafolla, Rosalyn A Juergens
PURPOSE: Non-small-cell lung cancer (NSCLC) has a large worldwide prevalence with a high mortality rate. Chemotherapy has offered modest improvements in survival over the past two decades. Immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has shown the promise of changing the future landscape of cancer therapy. This update reviews recent advances in the treatment of NSCLC with immune checkpoint modulation. METHODS: Publications and proceedings were identified from searching PubMed and proceedings from the annual meetings of the American Society of Clinical Oncology, European Society for Medical Oncology, and European Lung Cancer Conference...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#3
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426103/neurotoxicity-from-immune-checkpoint-inhibition-in-the-treatment-of-melanoma-a-single-centre-experience-and-review-of-the-literature
#4
L Spain, G Walls, M Julve, K O'Meara, T Schmid, E Kalaitzaki, S Turajlic, M Gore, J Rees, J Larkin
Background: Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase III trials. Immune-related neurological toxicity of varying severity has been reported in the literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab and pembrolizumab is reported as <1% in published clinical trials. We aimed to identify the incidence of neurotoxicity in our institution across anti-CTLA4 and anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425751/development-of-red-blood-cell-autoantibodies-following-treatment-with-checkpoint-inhibitors-a-new-class-of-anti-neoplastic-immunotherapeutic-agents-associated-with-immune-dysregulation
#5
Laura L Cooling, John Sherbeck, Jonathon C Mowers, Sheri L Hugan
Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28419328/efficacy-and-safety-of-osimertinib-in-a-japanese-compassionate-use-program
#6
Yutaka Fujiwara, Yasushi Goto, Shintaro Kanda, Hidehito Horinouchi, Noboru Yamamoto, Naomi Sakiyama, Reiko Ando Makihara, Yuichiro Ohe
Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets the T790M mutation of EGFR. In 2016, AstraZeneca conducted a compassionate use program for osimertinib in Japan. Methods: Eighteen consecutive patients with histologically proven non-small-cell lung cancer (NSCLC) and harboring the T790M EGFR mutation participated in the compassionate use program between 1 April and 25 May 2016, at the National Cancer Center Hospital...
April 13, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28419248/nivolumab-versus-everolimus-in-advanced-renal-cell-carcinoma-japanese-subgroup-analysis-from-the-checkmate-025-study
#7
Yoshihiko Tomita, Satoshi Fukasawa, Nobuo Shinohara, Hiroshi Kitamura, Mototsugu Oya, Masatoshi Eto, Kazunari Tanabe, Go Kimura, Junji Yonese, Masahiro Yao, Robert J Motzer, Hirotsugu Uemura, M Brent McHenry, Elmer Berghorn, Seiichiro Ozono
Background: Nivolumab improved overall survival (OS) and objective response rate (ORR) versus everolimus in previously treated patients with advanced renal cell carcinoma in the phase III CheckMate 025 study (minimum follow-up: 14 months). We report efficacy and safety in the global and Japanese populations (minimum follow-up: 26 months). Methods: Patients were randomized 1:1 to receive nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily...
April 13, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28419181/hyperprogression-during-anti-pd-1-pd-l1-therapy-in-patients-with-recurrent-and-or-metastatic-head-and-neck-squamous-cell-carcinoma
#8
E Saâda-Bouzid, C Defaucheux, A Karabajakian, V Palomar Coloma, V Servois, X Paoletti, C Even, J Fayette, J Guigay, D Loirat, F Peyrade, M Alt, J Gal, C Le Tourneau
Background: HASH(0x3b3e958) Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK). Patients and Methods: HASH(0x35c39c0) We retrospectively compared TGK on immunotherapy and TGK on last treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four French centers...
April 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28419059/late-onset-nivolumab-mediated-pneumonitis-in-a-patient-with-melanoma-and-multiple-immune-related-adverse-events
#9
Panagiotis T Diamantopoulos, Maria Gaggadi, Eva Kassi, Olga Benopoulou, Amalia Anastasopoulou, Helen Gogas
Immune-related adverse effects (AEs) of PD-1 inhibitors can affect almost every organ, but the skin, intestine, lung, eye, and liver are the most commonly affected organs. Here, we present the case of a 62-year-old female patient with stage IIIc melanoma treated with nivolumab in an adjuvant setting who sequentially developed hyperthyroidism, hypothyroidism, acute hepatitis, and pneumonitis. Six months before the emergence of pneumonitis, the patient had discontinued treatment with nivolumab because of acute hepatitis...
April 17, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28418115/aggravation-of-diabetes-and-incompletely-deficient-insulin-secretion-in-a-case-with-type-1-diabetes-resistant-hla-drb1-15-02-treated-with-nivolumab
#10
Kimio Matsumura, Kaoru Nagasawa, Yoichi Oshima, Shouta Kikuno, Kyohei Hayashi, Akihiro Nishimura, Minoru Okubo, Hironori Uruga, Kazuma Kishi, Tetsuro Kobayashi, Yasumichi Mori
Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse effects especially in endocrine systems. Several cases of acute onset insulin-dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of these cases have a susceptible HLA genotype for type 1 diabetes possibly suggesting that human leukocyte antigen (HLA) might be involved in the onset of diabetes with anti PD-1 therapy. We describe an atypical case of hyperglycemia after anti PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes and steroid diabetes was administered nivolumab three times for chemoresistant adenocarcinoma of the lung...
April 18, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28417343/adjuvant-therapy-for-melanoma
#11
REVIEW
Aya Agha, Ahmad A Tarhini
Systemic adjuvant therapy for surgically resected cutaneous melanoma that is at high risk for disease recurrence and death targets residual micrometastatic disease which is the source of future local or distant relapse. Interferon-alfa (IFNα) has been the most extensively studied in regimens that varied by dosage, route of administration, formulation, and duration of therapy. Most regimens have demonstrated improvements in relapse-free survival (RFS), while the regimen administered at high dosage (HDI) showed improvements in overall survival (OS) in two out of three RCTs...
May 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28416123/immune-checkpoint-inhibitors-for-patients-with-advanced-non-small-cell-lung-cancer-a%C3%A2-systematic-review
#12
REVIEW
Peter M Ellis, Emily T Vella, Yee C Ung
Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC...
February 16, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#13
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28410865/treatment-beyond-progression-in-patients-with-advanced-renal-cell-carcinoma-treated-with-nivolumab-in-checkmate-025
#14
Bernard Escudier, Robert J Motzer, Padmanee Sharma, John Wagstaff, Elizabeth R Plimack, Hans J Hammers, Frede Donskov, Howard Gurney, Jeffrey A Sosman, Pawel G Zalewski, Ulrika Harmenberg, David F McDermott, Toni K Choueiri, Martin Richardet, Yoshihiko Tomita, Alain Ravaud, Justin Doan, Huanyu Zhao, Helene Hardy, Saby George
BACKGROUND: Response patterns to nivolumab differ from those seen with other approved targeted therapies. OBJECTIVE: To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors) RECIST progression. DESIGN, SETTING, AND PARTICIPANTS: This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study...
April 12, 2017: European Urology
https://www.readbyqxmd.com/read/28408617/treatment-paradigms-for-advanced-non-small-cell-lung-cancer-at-academic-medical-centers-involvement-in-clinical-trial-endpoint-design
#15
Charu Aggarwal, Hossein Borghaei
Based on the positive results of various clinical trials, treatment options for non-small cell lung cancer (NSCLC) have expanded greatly over the last 25 years. While regulatory approvals of chemotherapeutic agents for NSCLC have largely been based on improvements in overall survival, recent approvals of many targeted agents for NSCLC (afatinib, crizotinib, ceritinib, osimertinib) have been based on surrogate endpoints such as progression-free survival and objective response. As such, selection of appropriate clinical endpoints for examining the efficacy of investigational agents for NSCLC is of vital importance in clinical trial design...
April 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28407622/prolactin-as-a-potential-early-predictive-factor-in-metastatic-non-small-cell-lung-cancer-patients-treated-with-nivolumab
#16
Salvatore Caponnetto, Giovanni Maria Iannantuono, Giacomo Barchiesi, Valentina Magri, Alain Gelibter, Enrico Cortesi
BACKGROUND/AIMS: Prolactin (PRL) is a peptide hormone and several studies have demonstrated its role as a cytokine in human T cell-mediated immunity. We are unaware if PRL is a positive or negative immunomodulator, but its effects on the regulation of T cells could inhibit the antitumor activity elicited by nivolumab (NIVO). We aimed to assess whether the occurrence of hyperprolactinemia in metastatic non-small cell lung cancer (mNSCLC) patients treated with NIVO is associated with poor clinical outcomes...
April 14, 2017: Oncology
https://www.readbyqxmd.com/read/28407528/immunotherapy-revolutionises-non-small-cell-lung-cancer-therapy-results-perspectives-and-new-challenges
#17
REVIEW
Etienne Giroux Leprieur, Coraline Dumenil, Catherine Julie, Violaine Giraud, Jennifer Dumoulin, Sylvie Labrune, Thierry Chinet
Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10...
April 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28407039/tumor-immune-microenvironment-and-nivolumab-efficacy-in-egfr-mutation-positive-non-small-cell-lung-cancer-based-on-t790m-status-after-disease-progression-during-egfr-tki-treatment
#18
K Haratani, H Hayashi, T Tanaka, H Kaneda, Y Togashi, K Sakai, K Hayashi, S Tomida, Y Chiba, K Yonesaka, Y Nonagase, T Takahama, J Tanizaki, K Tanaka, T Yoshida, K Tanimura, M Takeda, H Yoshioka, T Ishida, T Mitsudomi, K Nishio, K Nakagawa
Background.: The efficacy of programmed death-1 (PD-1) blockade in epidermal growth factor receptor gene ( EGFR ) mutation-positive non-small cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR . Patients and Methods.: We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A)...
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28403786/immune-checkpoint-inhibitors-and-cardiac-toxicity-an-emerging-issue
#19
Gilda Varricchi, Giancarlo Marone, Valentina Mercurio, Maria Rosaria Galdiero, Domenico Bonaduce, Carlo G Tocchetti
Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Cancer immunotherapies over the last years have revolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis...
April 7, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28403496/-interdisciplinary-recommendations-for-the-treatment-of-metastatic-renal-cell-carcinoma
#20
Kurt Miller, Lothar Bergmann, Christian Doehn, Jürgen Gschwend, Ulrich Keilholz
Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure...
February 2017: Aktuelle Urologie
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