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Richard J Lin, Catherine S Diefenbach
Hodgkin lymphoma is a unique disease entity characterized by a low number of neoplastic tumor cells surrounded by an inflammatory microenvironment composed of dysfunctional immune cells. Recent molecular and genetic studies have revealed that upregulation of the immune checkpoint pathway programmed death 1/programmed death ligand 1 is a key oncogenic driver of Hodgkin lymphoma. Corroborating these mechanistic studies, early-phase clinical trials using the checkpoint inhibitors nivolumab and pembrolizumab in treatment regimens for relapsed and/or refractory Hodgkin lymphoma have demonstrated impressive response rates, a promising durability of response, and a favorable side-effect profile...
October 15, 2016: Oncology (Williston Park, NY)
Holger Hebart, Peter Lang, Wilhelm Woessmann
No abstract text is available yet for this article.
October 18, 2016: Annals of Internal Medicine
Guoliang Pi, Hanping He, Jianping Bi, Ying Li, Yanping Li, Yong Zhang, Mingwei Wang, Guang Han, Chi Lin
INTRODUCTION: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown...
October 2016: Medicine (Baltimore)
Zhaohui Jin, Harry H Yoon
Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastro-esophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors. Both agents yielded a median duration of response lasting ~6-7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade...
October 2016: Journal of Gastrointestinal Oncology
Sanjay Tanday
No abstract text is available yet for this article.
October 13, 2016: Lancet Oncology
Jéssica Ribeiro Gomes, Rafael A Schmerling, Carolina K Haddad, Douglas J Racy, Robson Ferrigno, Erlon Gil, Pedro Zanuncio, Antônio C Buzaid
Abscopal effect is a rare phenomenon characterized by tumor regression of untreated metastatic lesions after a local therapy (eg, radiotherapy). We studied the probability of abscopal effect with radiotherapy associated with anti-programmed death cell 1 (PD1) therapy after progression on anti-PD1. This study is a retrospective analysis of patients treated with nivolumab or pembrolizumab for melanoma, non-small cell lung cancer (NSCLC) and renal cancer at Antônio Ermírio de Moraes Oncology Center, Brazil. To be eligible for this analysis, patients must have had unequivocal evidence of disease progression on anti-PD1 therapy and subsequent radiotherapy for any tumor site while still receiving anti-PD1...
November 2016: Journal of Immunotherapy
H Móciková, J Marková, Ľ Gahérová, Z Král, A Sýkorová, D Belada, V Procházka, L Martinková, T Papajík, T Kozák
High-dose chemotherapy with autologous stem cell transplantation remains the current standard of treatment for young patients with Hodgkin lymphoma in first relapse or in those who are refractory to first-line treatment. The most important prognostic factors in relapses are clinical stage IV, poor performance status, bulky mass, and less than partial remission after salvage chemotherapy. Standard salvage chemotherapy in relapse before autologous transplantation has not been defined; however, DHAP and ICE are most frequently used in this setting...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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
M Arenbergerova, I Mrazova, J Horazdovsky, E Sticova, A Fialova, P Arenberger
Vemurafenib is a selective inhibitor of the BRAF-kinase approved for the treatment of metastatic melanoma harboring BRAF mutation. Skin toxicity, including maculopapular exanthema, photosensitivity and keratoacanthoma, are the most common treatment-related adverse events of vemurafenib, affecting more than 90% of patients (1,2). It rarely presents with intense severity, with less than 1% of grade-4 toxicities reported in clinical trials (3,4). This article is protected by copyright. All rights reserved.
October 14, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Egle Ramelyte, Sabrina A Schindler, Reinhard Dummer
Introduction The introduction of immunotherapies into clinical practice has substantially improved the prognosis of metastatic melanoma patients as well as patients suffering from other cancers. The two FDA-approved checkpoint inhibitors against PD-1 (nivolumab and pembrolizumab) have been shown to significantly improve patient survival while being less toxic than previous treatment options. Areas covered The current scientific literature on safety and adverse events (AEs) related to anti-PD-1 therapies has been investigated with special attention to case reports and to the latest results announced at the major clinical cancer and melanoma meetings, including ASCO (American Society of Clinical Oncology), ESMO (European Society of medical Oncology) and EADO (European Association of Dermato-Oncology) annual meetings...
October 13, 2016: Expert Opinion on Drug Safety
Koji Takeda, Haruko Daga
On December 12, 2014, the U.S. Food and Drug Administration (FDA) approved ramucirumab for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Areas covered: This review discusses the best treatment strategy for ramucirumab, a vascular endothelial growth factor receptor-2 inhibitor for patients with advanced NSCLC. Expert opinion: The addition of ramucirumab to docetaxel in the treatment of patients with metastatic NSCLC who have progressed on or after platinum-based chemotherapy confers a 1...
October 13, 2016: Expert Opinion on Biological Therapy
Padmanee Sharma, Margaret K Callahan, Petri Bono, Joseph Kim, Pavlina Spiliopoulou, Emiliano Calvo, Rathi N Pillai, Patrick A Ott, Filippo de Braud, Michael Morse, Dung T Le, Dirk Jaeger, Emily Chan, Chris Harbison, Chen-Sheng Lin, Marina Tschaika, Alex Azrilevich, Jonathan E Rosenberg
BACKGROUND: Few effective treatments exist for patients with advanced urothelial carcinoma that has progressed after platinum-based chemotherapy. We assessed the activity and safety of nivolumab in patients with locally advanced or metastatic urothelial carcinoma whose disease progressed after previous platinum-based chemotherapy. METHODS: In this phase 1/2, multicentre, open-label study, we enrolled patients (age ≥18 years) with urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra at 16 sites in Finland, Germany, Spain, the UK, and the USA...
October 7, 2016: Lancet Oncology
Xi Zhang, Yuge Ran, Kunjie Wang, Yuanxue Zhu, Jinghua Li
PURPOSE: Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors. METHODS: PubMed, Embase, and oncology conference proceedings were searched for relevant studies...
2016: Drug Design, Development and Therapy
Christian Manegold, Anne-Marie C Dingemans, Jhanelle E Gray, Kazuhiko Nakagawa, Marianne Nicolson, Solange Peters, Martin Reck, Yi-Long Wu, Odd Terje Brustugun, Lucio Crino, Enriqueta Felip, Dean Fennell, Pilar Garrido, Rudolf M Huber, Aurelien Marabelle, Marcin Moniuszko, Francoise Mornex, Silvia Novello, Mauro Papotti, Maurice Pérol, Egbert F Smit, Kostas Syrigos, Jan P van Meerbeeck, Nico van Zandwijk, James Chih-Hsin Yang, Caicun Zhou, Everett Vokes
Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced non-small cell lung cancer (NSCLC), particularly those who have progressed on or during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab and nintedanib). It is hypothesised that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments...
October 8, 2016: Journal of Thoracic Oncology
Takaya Komori, Tetsuya Honda, Hiroyuki Irie, Atsushi Otsuka, Kenji Kabashima
is missing (Short communication).
October 10, 2016: Acta Dermato-venereologica
Robert L Ferris, George Blumenschein, Jerome Fayette, Joel Guigay, A Dimitrios Colevas, Lisa Licitra, Kevin Harrington, Stefan Kasper, Everett E Vokes, Caroline Even, Francis Worden, Nabil F Saba, Lara C Iglesias Docampo, Robert Haddad, Tamara Rordorf, Naomi Kiyota, Makoto Tahara, Manish Monga, Mark Lynch, William J Geese, Justin Kopit, James W Shaw, Maura L Gillison
Background Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. Methods In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab)...
October 8, 2016: New England Journal of Medicine
Jiaxing Huang, Yaxiong Zhang, Jin Sheng, Hongyu Zhang, Wenfeng Fang, Jianhua Zhan, Ting Zhou, Ying Chen, Lin Liu, Li Zhang
BACKGROUND: Nivolumab (BMS-936558/ONO-4538) was the first monoclonal antibody targeting programmed death (PD)-1. So far, a number of clinical trials on nivolumab have showed satisfactory efficacy in treating non-small-cell lung cancer (NSCLC). Herein, we present a meta-analysis evaluating the efficacy and safety of nivolumab for previously treated advanced NSCLC patients. METHODS: Electronic databases were searched for eligible literature. Data of objective response rate (ORR), disease control rate, overall survival, progression-free survival, and adverse effects (AEs) were extracted and pooled...
2016: OncoTargets and Therapy
Wataru Munakata, Ken Ohashi, Nobuhiko Yamauchi, Kensei Tobinai
We report the case of a patient with relapsed classical Hodgkin lymphoma who developed fulminant type I diabetes mellitus as a severe adverse event of treatment with the anti-programmed cell death-1 (PD-1) antibody, nivolumab. On the first day of the sixth cycle, the blood glucose level was markedly elevated (375 mg/dL). Although neither ketoacidosis nor ketonuria was detected, the markedly acute onset of the hyperglycemia was consistent with the typical clinical course of fulminant type I diabetes mellitus, and this diagnosis was supported by clinical data...
October 1, 2016: International Journal of Hematology
Alessia Mennitto, Paolo Grassi, Raffaele Ratta, Elena Verzoni, Michele Prisciandaro, Giuseppe Procopio
Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α)...
October 2016: Therapeutic Advances in Urology
Yuh-Min Chen
Immune checkpoint inhibition with blocking antibodies that target cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the programmed cell death protein 1 (PD-1) pathway [PD-1/programmed death-ligand 1 (PD-L1)] have demonstrated promise in a variety of malignancies. While ipilimumab has been approved as a CTLA-4 blocking antibody by the US Food and Drug Administration for the treatment of advanced melanoma, it is still not approved for lung cancer treatment. In contrast, nivolumab and pembrolizumab, both PD-1 blocking antibodies, have been approved for second-line treatment of nonsmall cell lung cancer in 2015 because of their high potency and long-lasting effects in some patient subgroups...
September 29, 2016: Journal of the Chinese Medical Association: JCMA
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