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anti pd 1 melanoma

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
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
Alpaslan Ozgun, Vernon K Sondak, Joseph Markowitz
No abstract text is available yet for this article.
August 22, 2016: Chinese Clinical Oncology
Leila Khoja, Minnie Kibiro, Ur Metser, Craig Gedye, David Hogg, Marcus O Butler, Eshetu G Atenafu, Anthony M Joshua
BACKGROUND: Radiological assessment of response to checkpoint inhibitors remains imperfect. We evaluated individual lesion and inter-patient response by response evaluation (RECIST) 1.1, immune-related response criteria (irRC), CHOI and modified CHOI (mCHOI) and correlated response with overall survival (OS). METHODS: Thirty-seven patients with 567 measurable lesions treated with pembrolizumab in the Keynote 001 trial were studied. Association of response with OS was determined...
October 4, 2016: British Journal of Cancer
A M Menzies, D B Johnson, S Ramanujam, V G Atkinson, A N M Wong, J J Park, J L McQuade, A N Shoushtari, K K Tsai, Z Eroglu, O Klein, J C Hassel, J A Sosman, A Guminski, R J Sullivan, A Ribas, M S Carlino, M A Davies, S K Sandhu, G V Long
BACKGROUND: Anti-PD-1 antibodies (anti-PD-1) have clinical activity in a number of malignancies. All clinical trials have excluded patients with significant preexisting autoimmune disorders (ADs), and only one has included patients with immune-related adverse events (irAEs) with ipilimumab. We sought to explore the safety and efficacy of anti-PD-1 in such patients. PATIENTS AND METHODS: Patients with advanced melanoma and preexisting ADs and/or major immune-related adverse events (irAEs) with ipilimumab (requiring systemic immunosuppression) that were treated with anti-PD-1 between 1(st) July 2012 and 30(th) September 2015 were retrospectively identified...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Tengfei Zhang, Jing Xie, Seiji Arai, Liping Wang, Xuezhong Shi, Ni Shi, Fen Ma, Sen Chen, Lan Huang, Li Yang, Wang Ma, Bin Zhang, Weidong Han, Jianchuan Xia, Hu Chen, Yi Zhang
PURPOSE: To systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer. RESULTS: Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53-2.41), 21% (95% CI: 17%-25%) and 21% (95% CI: 16%-27%) respectively. While the overall adverse effects rate for melanoma, NSCLC, RCC were 16% (95% CI: 6%-28%), 11% (95% CI: 8%-14%) and 20% (95% CI: 11%-32%) respectively...
September 24, 2016: Oncotarget
K A Ahmed, Y A Abuodeh, C Hogue, D G Stallworth, A O Naghavi, S Kim, S Sarangkasiri, P A S Johnstone, H M Yu, N I Khushalani, A B Etame, L B Harrison, J J Caudell
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
A C Olson, K Patel, Y M Mowery, J Wynne, N Ready, J P Kirkpatrick, A K Salama, M K Khan
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Douglas B Johnson, Garrett M Frampton, Matthew J Rioth, Erik Yusko, Yaomin Xu, Xingyi Guo, Riley C Ennis, David Fabrizio, Zachary R Chalmers, Joel Greenbowe, Siraj M Ali, Sohail Balasubramanian, James X Sun, Yuting He, Dennie T Frederick, Igor Puzanov, Justin M Balko, Justin M Cates, Jeffrey S Ross, Catherine Sanders, Harlan Robins, Yu Shyr, Vincent Miller, Philip J Stephens, Ryan J Sullivan, Jeffrey A Sosman, Christine M Lovly
Therapeutic antibodies blocking programmed death-1 and its ligand (PD-1/PD-L1) induce durable responses in a substantial fraction of melanoma patients. We sought to determine whether the number and/or type of mutations identified using a next generation sequencing (NGS) panel available in the clinic were correlated with response to anti-PD-1 in melanoma. Using archival melanoma samples from anti-PD-1/PD-L1-treated patients, we performed hybrid capture-based NGS on 236-315 genes and T-cell receptor (TCR) sequencing on initial and validation cohorts from two centers...
September 26, 2016: Cancer Immunology Research
Emily F Goode, Elizabeth C Smyth
Survival for patients with advanced oesophageal and stomach cancer is poor; together these cancers are responsible for more than a million deaths per year globally. As chemotherapy and targeted therapies such as trastuzumab and ramucirumab result in modest improvements in survival but not long-term cure for such patients, development of alternative treatment approaches is warranted. Novel immunotherapy drugs such as checkpoint inhibitors have been paradigm changing in melanoma, non-small cell lung cancer and urothelial cancers...
September 22, 2016: Journal of Clinical Medicine
Gregory S Alexander, Joshua D Palmer, Madalina Tuluc, Jianqing Lin, Adam P Dicker, Voichita Bar-Ad, Larry A Harshyne, Jennifer Louie, Colette M Shaw, D Craig Hooper, Bo Lu
BACKGROUND: Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1). Pembrolizumab and other immunocheckpoint-blocking monoclonal antibodies work by modulating a patient's own immune system to increase anti-tumor activity. While immunocheckpoint blockade has shown promising results, only 20-40 % of patients experience objective clinical benefit. Differences in individual tumor biology and the presence multiple immune checkpoints present a challenge for treatment...
2016: Journal of Hematology & Oncology
Stefan Diem, Fabienne Keller, Reinhard Rüesch, Samia A Maillard, Daniel E Speiser, Reinhard Dummer, Marco Siano, Ursula Urner-Bloch, Simone M Goldinger, Lukas Flatz
Immunotherapy leads to significantly prolonged survival of patients with metastatic melanoma. Autoimmune side effects including colitis, dermatitis, and endocrine abnormalities are common in patients treated with ipilimumab [anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4)]. Antibodies such as pembrolizumab that interfere with the PD-1 (programmed cell death 1)/PD-L1 pathway show greater efficacy and less toxicity than ipilimumab. Here we report 2 cases of pembrolizumab-induced uveitis associated with complete or partial tumor response...
November 2016: Journal of Immunotherapy
Jarushka Naidoo, Xuan Wang, Kaitlin M Woo, Tunc Iyriboz, Darragh Halpenny, Jane Cunningham, Jamie E Chaft, Neil H Segal, Margaret K Callahan, Alexander M Lesokhin, Jonathan Rosenberg, Martin Voss, Charles M Rudin, Hira Rizvi, Xue Hou, Katherine Rodriguez, Melanie Albano, Ruth-Ann Gordon, Charles Leduc, Natasha Rekhtman, Bianca Harris, Alexander M Menzies, Alexander D Guminski, Matteo S Carlino, Benjamin Y Kong, Jedd D Wolchok, Michael A Postow, Georgina V Long, Matthew D Hellmann
PURPOSE: Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. METHODS: Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015)...
September 19, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Shalin Shah, James E Ward, Riyue Bao, Curtis R Hall, Bruce E Brockstein, Jason J Luke
Anti-Programed Death 1 (PD-1) is standard immunotherapy for multiple cancers and the expression of one of its ligands, PD-L1, has been described in germ cell tumors (GCTs). Neither the clinical activity of anti-PD-1 nor the incidence of an immunoresponsive tumor microenvironment has been described for GCTs. A patient initially diagnosed with melanoma via fine needle aspiration was treated with one dose of antibody to PD-1. A core needle biopsy was subsequently performed to acquire sufficient tissue for molecular analysis, which led to a change in diagnosis to metastatic embryonal carcinoma...
September 16, 2016: Cancer Immunology Research
K A Ahmed, Y A Abuodeh, M I Echevarria, J A Arrington, D G Stallworth, C Hogue, A O Naghavi, S Kim, Y Kim, B G Patel, S Sarangkasiri, P A S Johnstone, S Sahebjam, N I Khushalani, P A Forsyth, L B Harrison, M Yu, A B Etame, J J Caudell
BACKGROUND: The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single-session stereotactic radiosurgery (SRS) and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. PATIENTS AND METHODS: Patients were included if MBMs were treated with single-session SRS within 3 months of receiving systemic therapy...
September 15, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Yasuhiro Nakamura, Yukiko Teramoto, Yuri Asami, Taisuke Matsuya, Akifumi Yamamoto
Recently developed immune checkpoint inhibitors, such as anti-PD-1 antibodies, have shown a clear improvement in clinical efficacy compared with conventional cytotoxic chemotherapy in the treatment of patients with advanced melanoma. Treatment with anti-PD-1 antibodies has resulted in improved objective response rates, longer durations of response, and longer overall survival rates. Although the incidence rate of adverse events associated with anti-PD-1 antibodies is lower than that associated with cytotoxic agents, characteristic severe adverse events such as pneumonia, endocrinopathy, and colitis can occur...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Hisae Iinuma, Noriyuki Matsutani, Hirofumi Uehara, Masafumi Kawamura
The superior therapeutic effects of antibodies targeting immune checkpoints have been reported in the treatment of various cancers including non-small cell lung cancer(NSCLC)and malignant melanoma. However, the risk of reactivity against selfantigens and the high prices of these drugs are major concerns. Previously, PD-L1 protein expression and the number of infiltrating T cells in tumor tissues were investigated by immunohistochemical staining, as biomarkers for therapeutic anti-PD- 1 antibodies. However, further research into the clinical significance of PD-L1 expression in tumor tissues is still required...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Maria Monica Talag, Mohamed Alsharedi, Nadim Bou Zgheib, Yehuda Lebowicz
Recent advances in novel immunotherapeutic and targeted therapeutic agents have increased treatment options in patients with advanced metastatic melanoma. However, evidence in the literature on whether or not extracutaneous melanoma will acquire an equivalent advantage from these therapies is very scarce. In general, extracutaneous melanomas are rare and aggressive melanomas, which are clinically and biologically unique, with higher incidence of metastatic disease and poor prognosis. In this case report, we present a very rare case of a 54-year-old woman with primary pelvic retroperitoneal melanoma treated with an anti-PD-1 antibody, pembrolizumab...
2016: BMJ Case Reports
F Stephen Hodi, Jason Chesney, Anna C Pavlick, Caroline Robert, Kenneth F Grossmann, David F McDermott, Gerald P Linette, Nicolas Meyer, Jeffrey K Giguere, Sanjiv S Agarwala, Montaser Shaheen, Marc S Ernstoff, David R Minor, April K Salama, Matthew H Taylor, Patrick A Ott, Christine Horak, Paul Gagnier, Joel Jiang, Jedd D Wolchok, Michael A Postow
BACKGROUND: Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma...
September 9, 2016: Lancet Oncology
Djoke Hendriks, Yuan He, Iris Koopmans, Valerie R Wiersma, Robert J van Ginkel, Douwe F Samplonius, Wijnand Helfrich, Edwin Bremer
Antibodies that block PD-L1/PD-1 immune checkpoints restore the activity of functionally-impaired antitumor T cells. These antibodies show unprecedented clinical benefit in various advanced cancers, particularly in melanoma. However, only a subset of cancer patients responds to current PD-L1/PD-1-blocking strategies, highlighting the need for further advancements in PD-L1/PD-1-based immunotherapy. Here, we report on a novel approach designed to combine PD-L1 checkpoint inhibition with the tumor-selective induction of apoptosis by TNF-related Apoptosis Inducing Ligand (TRAIL)...
August 2016: Oncoimmunology
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