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Clinical trial metastatic melanoma

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https://www.readbyqxmd.com/read/28717400/treatment-of-nras-mutated-advanced-or-metastatic-melanoma-rationale-current-trials-and-evidence-to-date
#1
REVIEW
Amélie Boespflug, Julie Caramel, Stephane Dalle, Luc Thomas
The disease course of BRAF (v-raf murine sarcoma viral oncogene homolog B1)-mutant melanoma has been drastically improved by the arrival of targeted therapies. NRAS (neuroblastoma RAS viral oncogene homolog)-mutated melanoma represents 15-25% of all metastatic melanoma patients. It currently does not have an approved targeted therapy. Metastatic patients receive immune-based therapies as first-line treatments, then cytotoxic chemotherapy like carboplatin/paclitaxel (C/P), dacarbazine (DTIC) or temozolomide (TMZ) as a second-line treatment...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28715649/excellent-response-to-anti-pd-1-therapy-in-a-patient-with-hepatocellular-carcinoma-case-report-and-review-of-literature
#2
Hirva Mamdani, Howard Wu, Bert H O'Neil, Amikar Sehdev
Hepatocellular carcinoma (HCC) is an aggressive cancer associated with high mortality worldwide. HCC develops in the setting of underlying cirrhosis due to chronic liver disease. Surgery is usually considered the treatment of choice for early disease; however, most patients have locally advanced or metastatic HCC at diagnosis in which case treatments are limited. Immune checkpoint blockade of programmed death receptor-1 (PD-1) pathway offers a potential treatment strategy based on the encouraging results of the phase I/II trial of nivolumab (Checkmate 040 trial)...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28707167/supportive-care-for-patients-undergoing-immunotherapy
#3
Bernardo Leon Rapoport, Ronwyn van Eeden, Vincent Sibaud, Joel B Epstein, Jean Klastersky, Matti Aapro, Devan Moodley
Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections...
July 13, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28690944/acute-inflammatory-demyelinating-polyneuroradiculopathy-with-ipilimumab-in-metastatic-melanoma-a-case-report-and-review-of-literature
#4
Chintan Rupareliya, Syeda Naqvi, Vishal B Jani
Ipilimumab (Bristol-Myers Squibb Co., New York, NY) is a novel anticancer medication used for the treatment of metastatic melanoma. The exact mechanism of its action remains unclear; however, data from previous clinical trials postulates the immunomodulatory activity of ipilimumab to enhance therapeutic effectiveness. Ipilimumab was approved by the Food and Drug Administration (FDA) in March 2011 for use in stage III and IV of unresectable metastatic melanoma. We report a single case of acute inflammatory demyelinating polyneuroradiculopthy (AIDP) in the patient treated with ipilimumab for recurrent metastatic melanoma...
June 5, 2017: Curēus
https://www.readbyqxmd.com/read/28679643/endogenous-heat-shock-protein-induction-with-or-without-radiofrequency-ablation-or-cryoablation-in-patients-with-stage-iv-melanoma
#5
Evidio Domingo-Musibay, James M Heun, Wendy K Nevala, Matthew Callstrom, Thomas Atwell, Evanthia Galanis, Lori A Erickson, Svetomir N Markovic
LESSONS LEARNED: Percutaneous thermal ablation combined with in situ granulocyte-macrophage colony-stimulating factor cytokine therapy was technically feasible and well tolerated.No significant clinical or immunologic responses were seen. BACKGROUND: Melanoma tumor-derived heat-shock proteins (HSPs) and HSP-peptide complexes can elicit protective antitumor responses. The granulocyte-macrophage colony-stimulating factor (GM-CSF) chemokine can also promote uptake and processing by professional antigen presenting cells (APCs)...
July 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28679287/the-safety-of-nivolumab-for-the-treatment-of-metastatic-melanoma
#6
James Larkin, Aine O'Reilly
Nivolumab, a human IgG4 monoclonal antibody directed against PD-1, is a checkpoint inhibitor that is licenced in the treatment of metastatic melanoma either as a monotherapy or in combination with ipilimumab, a CTLA-4 inhibitor. The introduction of immune checkpoint inhibitors to the therapeutic landscape has dramatically altered outcomes in a proportion of patients with metastatic melanoma. Immune checkpoint inhibitors result in a toxicity profile that is distinct from that of chemotherapy or targeted therapy based on their immunomodulatory mechanism and similarly can result in patterns of response that are unique...
July 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28678032/therapeutic-oncolytic-viruses-clinical-advances-and-future-directions
#7
Susanne G Warner, Michael P O'Leary, Yuman Fong
PURPOSE OF REVIEW: The present review will highlight recent advances in the clinical application of oncolytic viral therapy. RECENT FINDINGS: Until recently, oncolytic viral researchers saw the immune system as an enemy that would clear the virus from the bloodstream. However, researchers now understand that sustained responses are seen in those patients with more robust antitumor immune responses. Much of the current focus in oncolytic viral research is trained on manipulation of the immune system to affect cancer cell killing in the tumor microenvironment and to facilitate durable systemic antitumor immunity...
July 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28668095/cspg4-a-prototype-oncoantigen-for-translational-immunotherapy-studies
#8
REVIEW
Valeria Rolih, Giuseppina Barutello, Selina Iussich, Raffaella De Maria, Elena Quaglino, Paolo Buracco, Federica Cavallo, Federica Riccardo
Thanks to striking progress in both the understanding of anti-tumor immune response and the characterization of several tumor associated antigens (TAA), a more rational design and more sophisticated strategies for anti-tumor vaccination have been possible. However, the effectiveness of cancer vaccines in clinical trial is still partial, indicating that additional studies are needed to optimize their design and their pre-clinical testing. Indeed, anti-tumor vaccination success relies on the choice of the best TAA to be targeted and on the translational power of the pre-clinical model used to assess its efficacy...
July 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28665153/risk-of-peripheral-edema-in-cancer-patients-treated-with-mek-inhibitors-a-systematic-review-and-meta-analysis-of-clinical-trials
#9
Yong Yang, Yi-Hua Liu, Xu Sun, Ming-Wei Yu, Lin Yang, Pei-Yu Cheng, Guo-Wang Yang, Xiao-Min Wang
BACKGROUND: MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors, however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors. MATERIAL AND METHODS: We searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials...
June 30, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28662283/treatment-of-a-patient-with-hiv-and-metastatic-melanoma-with-consecutive-ipilimumab-and-nivolumab
#10
D Tomsitz, R Hein, T Biedermann, J Kohlmeyer
Recently new therapeutic agents were developed leading to a paradigm shift in melanoma treatment by the approval of checkpoint inhibitors and targeted therapies. However, in clinical trials HIV-infected melanoma patients have been excluded due to their condition and no randomized double-blind placebo-controlled studies have been published to evaluate the efficacy of these therapies in melanoma patients with concomitant HIV infection. We report on a HIV-positive melanoma patient treated sequentially with ipilimumab and nivolumab whose CD4 count and virus replication have been monitored closely...
June 29, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28661584/clinical-and-palliative-care-outcomes-for-patients-of-poor-performance-status-treated-with-antiprogrammed-death-1-monoclonal-antibodies-for-advanced-melanoma
#11
Annie Wong, Molly Williams, Donna Milne, Kortnye Morris, Peter Lau, Odette Spruyt, Sonia Fullerton, Grant McArthur
BACKGROUND: Antiprogrammed death-1 antibodies (anti-PD1) have response rates of 40% in metastatic melanoma. Patients with poor performance status (PS) were excluded from clinical trials, yet use of anti-PD1 is widespread in clinical practice. Literature regarding clinical and palliative care outcomes in patients with poor PS treated with anti-PD1 is lacking. METHODS: Retrospective review of outcomes for all patients with advanced melanoma treated with anti-PD1 between 2012 and June 2015 at Peter MacCallum Cancer Centre, a tertiary specialist cancer center in Australia...
June 29, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28658143/efficacy-and-safety-of-anti-pd-1-and-anti-pd-1-combined-with-anti-ctla-4-immunotherapy-to-advanced-melanoma-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#12
REVIEW
Chunyan Hao, Jinhui Tian, Huiling Liu, Fei Li, Hongxia Niu, Bingdong Zhu
BACKGROUND: Anti-PD-1 monoclonal antibodies, nivolumab and pembrolizumab, and anti-CTLA-4 antibody ipilimumab are being in clinic trials to treat melanoma. Here, we performed a meta-analysis to evaluate the efficacy and toxicity of them against advanced melanoma. METHODS: Eleven reports from 6 randomized control trials on treating metastatic melanoma, which were divided into 3 subgroups, nivolumab/pembrolizumab versus chemotherapy, nivolumab versus ipilimumab, and nivolumab-plus-ipilimumab versus ipilimumab, were included and the meta-analysis was performed for each subgroup...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28654547/dendritic-cell-vaccination-for-metastatic-melanoma-a-14-year-monoinstitutional-experience
#13
Francesco de Rosa, Laura Ridolfi, Laura Fiammenghi, Massimiliano Petrini, Anna M Granato, Valentina Ancarani, Elena Pancisi, Valentina Soldati, Serena Cassan, Jenny Bulgarelli, Massimo Framarini, Francesca Tauceri, Giuseppe Migliori, Claudia Brolli, Giorgia Gentili, Elisabetta Petracci, Oriana Nanni, Angela Riccobon, Ruggero Ridolfi, Massimo Guidoboni
Although immunomodulating antibodies are highly effective in metastatic melanoma, their toxicity, related to the activation of T lymphocytes, can be severe. Anticancer vaccines promote a fairly specific response and are very well tolerated, but their effectiveness has yet to be demonstrated. We have been treating patients with advanced melanoma with an autologous dendritic cell vaccine since 2001; to better characterize the safety and efficacy of our product, we designed a retrospective study on all of our patients treated with the vaccine to date...
August 2017: Melanoma Research
https://www.readbyqxmd.com/read/28642816/safe-and-effective-administration-of-t-vec-in-a-patient-with-heart-transplantation-and-recurrent-locally-advanced-melanoma
#14
Gustavo Schvartsman, Kristen Perez, Jill E Flynn, Jeffrey N Myers, Hussein Tawbi
BACKGROUND: Immunotherapy plays a key role in the treatment of metastatic melanoma. Patients with autoimmune conditions and/or on immunosuppressive therapy due to orthotropic transplants, however, are systematically excluded from clinical trials. Talimogene laherparepvec (T-VEC) is the first oncolytic virus to be approved by the FDA for cancer therapy. To our knowledge, this is the first report of T-VEC being administered in the setting of an organ transplant recipient. CASE PRESENTATION: Here we present the case of a patient with recurrent locally advanced cutaneous melanoma receiving salvage T-VEC therapy in the setting of orthotropic heart transplantation...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28640512/a-major-responder-to-ipilimumab-and-nivolumab-in-metastatic-uveal-melanoma-with-concomitant-autoimmunity
#15
Pui Ying Chan, Peter Hall, Gordon Hay, Victoria M L Cohen, Peter W Szlosarek
The use of immune checkpoint inhibition has led to major improvements in outcome for patients with metastatic cutaneous melanoma. The combination of ipilimumab and nivolumab has demonstrated greater activity over single-agent immunotherapy in phase III trials. Clinical trials of combination CTLA-4 and PD-1 inhibition are underway in uveal melanoma, for which there are currently no data. Here, we present the case of a 74-year-old male patient with metastatic uveal melanoma, who was treated with a combination of ipilimumab and nivolumab...
June 22, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#16
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#17
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28601879/outcomes-in-melanoma-patients-treated-with-braf-mek-directed-therapy-or-immune-checkpoint-inhibition-stratified-by-clinical-trial-versus-standard-of-care
#18
Chloe Goldman, Jeremy Tchack, Eric M Robinson, Sung Won Han, Una Moran, David Polsky, Russell S Berman, Richard L Shapiro, Patrick A Ott, Iman Osman, Hua Zhong, Anna C Pavlick, Melissa Ann Wilson
OBJECTIVES: Since 2011, metastatic melanoma treatment has evolved with commercial approval of BRAF- and MEK-targeted therapy and CTLA-4- and PD-1-blocking antibodies (immune checkpoint inhibitors, ICI). While novel therapies have demonstrated improved prognosis in clinical trials, few studies have examined the evolution of prognosis and toxicity of these drugs among an unselected population. We assess whether survival and toxicity reported in trials, which typically exclude most patients with brain metastases and poor performance status, are recapitulated within a commercial access population...
June 10, 2017: Oncology
https://www.readbyqxmd.com/read/28592387/dabrafenib-plus-trametinib-in-patients-with-braf-v600-mutant-melanoma-brain-metastases-combi-mb-a-multicentre-multicohort-open-label-phase-2-trial
#19
Michael A Davies, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Keith T Flaherty, Ana Arance, Vanna Chiarion-Sileni, Luc Thomas, Thierry Lesimple, Laurent Mortier, Stergios J Moschos, David Hogg, Iván Márquez-Rodas, Michele Del Vecchio, Céleste Lebbé, Nicolas Meyer, Ying Zhang, Yingjie Huang, Bijoyesh Mookerjee, Georgina V Long
BACKGROUND: Dabrafenib plus trametinib improves clinical outcomes in BRAF(V600)-mutant metastatic melanoma without brain metastases; however, the activity of dabrafenib plus trametinib has not been studied in active melanoma brain metastases. Here, we report results from the phase 2 COMBI-MB trial. Our aim was to build on the current body of evidence of targeted therapy in melanoma brain metastases through an evaluation of dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases...
June 2, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28589078/recent-clinical-trials-of-cancer-immunogene-therapy-in-companion-animals
#20
REVIEW
Liliana M E Finocchiaro, Gerardo C Glikin
This mini-review presents the results of veterinary clinical trials on immunogene therapy published from 2014 to 2016. A variety of tumors, among them melanoma (canine and equine), mastocytoma (canine), mammary adenocarcinoma (canine) and fibrosarcoma (feline) were treated by using diverse strategies. Non-viral vectors were usually employed to transfer genes of cytokines, suicide enzymes and/or tumor associated antigens. In general terms, minor or no adverse collateral effects were related to these procedures, and treated patients frequently improved their conditions (better quality of life, delayed or suppressed recurrence or metastatic spread, increased survival)...
May 20, 2017: World Journal of Experimental Medicine
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