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Clinical trial metastatic melanoma

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https://www.readbyqxmd.com/read/29222604/model-based-analysis-of-the-heterogeneity-in-the-tumour-size-dynamics-differentiates-vemurafenib-dabrafenib-and-trametinib-in-metastatic-melanoma
#1
Hitesh B Mistry, David Orrell, Raluca Eftimie
PURPOSE: Explore the heterogeneity in dynamics of tumour response to vemurafenib, dabrafenib and trametinib using routinely collected clinical trial imaging data. METHODS: Time-series imaging data from the phase III studies of vemurafenib, dabrafenib and trametinib were collected through a data repository. A mathematical model based on basic mechanisms of tumour growth was placed within a statistical modelling framework to analyse the data. RESULTS: The analysis revealed: (1) existence of homogeneity in drug response and resistance development within a patient; (2) tumour shrinkage rate does not relate to rate of resistance development; (3) vemurafenib and dabrafenib, two BRAF inhibitors, have different variability in tumour shrinkage rates...
December 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29219612/nonprogression-with-avelumab-treatment-associated-with-gains-in-quality-of-life-in-metastatic-merkel-cell-carcinoma
#2
Howard L Kaufman, Matthias Hunger, Meliessa Hennessy, Michael Schlichting, Murtuza Bharmal
AIM: To assess the association between tumor response and health-related quality of life (HRQoL) in patients with metastatic Merkel cell carcinoma treated with the anti-PD-L1 avelumab. MATERIALS & METHODS: Phase II single-arm trial (NCT02155647) data of 88 patients were analyzed. Correlations between percentage reduction in tumor size and change from baseline in Functional Assessment of Cancer Therapy - General (FACT-G), FACT - Melanoma (FACT-M) and EuroQol-5 Dimension scores were calculated...
December 8, 2017: Future Oncology
https://www.readbyqxmd.com/read/29208646/a-serum-protein-signature-associated-with-outcome-after-anti-pd1-therapy-in-metastatic-melanoma
#3
Mario Sznol, Ryan J Sullivan, Shauna Blackmon, Genevieve Boland, Harriet M Kluger, Ruth Halaban, Antonella Bacchiocchi, Paolo A Ascierto, Marilena Capone, Carlos Oliveira, Krista Meyer, Julia Grigorieva, Senait G Asmellash, Joanna Roder, Heinrich Roder, Jeffrey S Weber
A mass spectrometry analysis was performed using serum from patients receiving checkpoint inhibitors to define baseline protein signatures associated with outcome in metastatic melanoma. Pre-treatment serum was obtained from a development set of 119 melanoma patients on a trial of nivolumab with or without a multi-peptide vaccine and from patients receiving pembrolizumab, nivolumab, ipilimumab, or both nivolumab and ipilimumab. Spectra were obtained using matrix assisted laser desorption/ionization time of flight mass spectrometry...
December 5, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29200112/epidemiology-treatment-and-complications-of-central-nervous-system-metastases
#4
Amy A Pruitt
PURPOSE OF REVIEW: Neurologic problems resulting from systemic cancer metastases to brain parenchyma, dura, spinal cord, and leptomeninges are among the most common types of consultations addressed by neurologists. With patients surviving longer from systemic cancer, along with the rapidly evolving therapeutic options, the treatment of these devastating complications has become both more effective and more complicated. This article reviews current patterns of metastatic disease and the increasingly nuanced landscape of evolving therapies, their complications, and their impact on quality of survival...
December 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29190182/checkpoint-inhibition-in-pediatric-hematologic-malignancies
#5
Kara L Davis, Archana M Agarwal, Anupam R Verma
Immune surveillance comprising of adaptive and innate immune systems is naturally designed to eliminate cancer development; overexpression of inhibitory receptors and their ligands prevent this check and lead to evasion and hence cancer progression and metastasis. The use of tumor-specific monoclonal antibodies (MAbs) targeting these checkpoint regulators is promising and has led to this novel field of cancer immunotherapy. The first antibody directed against cytotoxic T-lymphocyte associated protein 4 (CTLA-4), ipilimumab, showed promising results in clinical trials and was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011...
November 30, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29181212/uncommon-braf-mutations-associated-with-durable-response-to-immunotherapy-in-patients-with-metastatic-melanoma
#6
Brenen P Swofford, Jade Homsi
Melanoma is a disease process which has been increasing in incidence over the past three decades and metastatic melanoma carries a poor prognosis. Through genetic studies of this disease, it has been determined that the BRAF V600 mutation plays a major role in the pathophysiology of the disease and this has led to the utilization of targeted therapy (BRAF and MEK inhibitors) in its treatment. Other BRAF mutations (non-V600 mutations) are rare in melanoma and targeted therapy is not indicated for patients with these mutations due to reduced response rates...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29180872/therapeutic-efficacy-and-safety-of-combined-braf-and-mek-inhibition-in-patients-with-malignant-melanoma-a-meta-analysis
#7
Peng Chen, Fuchao Chen, Benhong Zhou
Background: Recent clinical studies have shown that initial therapy with combined BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibition is more effective in metastatic melanoma than single-agent BRAF inhibitors. However, the response rates with single-agent BRAF are low. Thus, the objective of this study was to conduct a meta-analysis of randomized controlled trials to compare the efficacy and adverse events risk between mono-therapy and combination therapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29180474/vitamin-c-sensitizes-melanoma-to-bet-inhibitors
#8
Gaofeng Wang, Sushmita Mustafi, Vladimir Camarena, Claude-Henry Volmar, Tyler C Huff, David W Sant, Shaun P Brothers, Zhao-Jun Liu, Claes Wahlestedt
Bromodomain and extra-terminal inhibitors (BETi) are promising cancer therapies, yet prominent side effects of BETi at effective doses have been reported in Phase I clinical trials. Here we screened a panel of small molecules targeting epigenetic modulators against human metastatic melanoma cells. Cells were pretreated with or without ascorbate (vitamin C), which promotes DNA demethylation and subsequently changes the sensitivity to drugs. Top hits were structurally unrelated BETi including JQ1, I-BET151, CPI-203, and BI-2536...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29177235/metastatic-melanoma-patients-sensitivity-to-ipilimumab-cannot-be-predicted-by-tumor-characteristics
#9
Kara Rossfeld, Erinn M Hade, Alexandra Gangi, Matthew Perez, Emily N Kinsey, Joanna Grabska, Ashley Ederle, Jonathan Zager, April K Salama, Thomas E Olencki, Georgia M Beasley
Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. However, not all patients respond to therapy and toxicities can be severe leaving need for reliable clinical predictive markers. Methods: We examined primary tumor characteristics including ulceration, BRAF mutation status, and Breslow depth in patients who subsequently developed stage IV disease and were treated with ipilimumab at 3 institutions. Patients in this study were not treated on clinical trials...
October 2017: International Journal of Surgery. Oncology
https://www.readbyqxmd.com/read/29177095/targeting-immune-checkpoints-in-breast-cancer-an-update-of-early-results
#10
REVIEW
Cinzia Solinas, Andrea Gombos, Sofiya Latifyan, Martine Piccart-Gebhart, Marleen Kok, Laurence Buisseret
The immune tumour microenvironment has been shown to play a crucial role in the development and progression of cancer. Expression of gene signatures, reflecting immune activation, and the presence of tumour-infiltrating lymphocytes were associated with favourable outcomes in HER2-positive and triple-negative breast cancer. Recently, immunotherapy with immune checkpoint blockade induced long-lasting responses and improved survival in hard-to-treat malignancies (ie, melanoma and non-small cell lung cancer) and are changing treatment paradigms in a variety of neoplastic diseases...
2017: ESMO Open
https://www.readbyqxmd.com/read/29177094/safety-and-immunogenicity-of-mage-a3-cancer-immunotherapeutic-with-dacarbazine-in-patients-with-mage-a3-positive-metastatic-cutaneous-melanoma-an-open-phase-i-ii-study-with-a-first-assessment-of-a-predictive-gene-signature
#11
Jean-Jacques Grob, Laurent Mortier, Lionel D'Hondt, Florent Grange, Jean Francois Baurain, Brigitte Dréno, Céleste Lebbe, Caroline Robert, Anne Dompmartin, Bart Neyns, Marc Gillet, Jamila Louahed, Silvija Jarnjak, Frédéric F Lehmann
Background: We assessed safety, immunogenicity and clinical activity of recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) in association with dacarbazine in patients with metastatic melanoma. Methods: In this open-label, phase I/II, uncontrolled multicentre trial conducted in Belgium and France, patients with MAGE-A3-positive melanoma received up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with eight doses of dacarbazine...
2017: ESMO Open
https://www.readbyqxmd.com/read/29157311/peripheral-and-local-predictive-immune-signatures-identified-in-a-phase-ii-trial-of-ipilimumab-with-carboplatin-paclitaxel-in-unresectable-stage-iii-or-stage-iv-melanoma
#12
Rahima Jamal, Réjean Lapointe, Eftihia Cocolakis, Paméla Thébault, Shirin Kazemi, Jennifer E Friedmann, Jeanne Dionne, Jean-François Cailhier, Karl Bélanger, Jean-Pierre Ayoub, Huy Le, Caroline Lambert, Jida El-Hajjar, Léon C van Kempen, Alan Spatz, Wilson H Miller
BACKGROUND: Checkpoint blockade with ipilimumab provides long-term survival to a significant proportion of patients with metastatic melanoma. New approaches to increase survival and to predict which patients will benefit from treatment are needed. This phase II trial combined ipilimumab with carboplatin/paclitaxel (CP) to assess its safety, efficacy, and to search for peripheral and tumor-based predictive biomarkers. METHODS: Thirty patients with untreated unresectable/metastatic melanoma were treated with ipilimumab and CP...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157300/prospects-for-combined-use-of-oncolytic-viruses-and-car-t-cells
#13
REVIEW
Adam Ajina, John Maher
With the approval of talimogene laherparepvec (T-VEC) for inoperable locally advanced or metastatic malignant melanoma in the USA and Europe, oncolytic virotherapy is now emerging as a viable therapeutic option for cancer patients. In parallel, following the favourable results of several clinical trials, adoptive cell transfer using chimeric antigen receptor (CAR)-redirected T-cells is anticipated to enter routine clinical practice for the management of chemotherapy-refractory B-cell malignancies. However, CAR T-cell therapy for patients with advanced solid tumours has proved far less successful...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29155424/immune-checkpoint-inhibitors-in-sarcomas-in-quest-of-predictive-biomarkers
#14
Robin Veenstra, Marie Kostine, Anne-Marie Cleton-Jansen, Noel Fcc de Miranda, Judith Vmg Bovée
Sarcomas are a rare group of tumors of mesenchymal origin. Metastatic sarcomas are often difficult to treat and unresponsive to standard radio- and chemotherapy, resulting in a poor survival rate for patients. Novel treatments with immune checkpoint inhibitors have been proven to prolong survival of patients with a variety of cancers, including metastatic melanoma, lung, and renal cell carcinoma. Since immune checkpoint inhibitors could provide a novel treatment option for patients with sarcomas, clinical trials investigating their efficacy in these group of tumors are ongoing...
November 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29149136/mapk-pathway-targeted-therapies-care-and-management-of-unique-toxicities-in-patients-with-advanced-melanoma%C3%A2
#15
Krista M Rubin
BACKGROUND: Agents targeting the MAPK pathway, including inhibitors of BRAF and MEK, have dramatically transformed the treatment landscape for patients with BRAF-mutant metastatic melanoma. Although generally well tolerated, targeted agents were associated with unique toxicities.
. OBJECTIVES: This article aims to provide nurses with an overview of the key toxicities and associated management strategies of the characteristic adverse event (AE) profile associated with agents targeting the MAPK pathway...
December 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29135115/effectiveness-and-safety-profile-of-ipilimumab-therapy-in-previously-treated-patients-with-unresectable-or-metastatic-melanoma-the-romanian-patient-access-program
#16
Dan Corneliu Jinga, Tudor Ciuleanu, Serban Negru, Ciprian Aldea, Laurentia Gales, Florin Bacanu, Cristina Oprean, Mihai Manolache, Daniela Zob, Stefan Curescu, Dana-Lucia Stanculeanu
PURPOSE: The Romanian Patient Access Program (Ro-PAP, CA 184-427), part of the European Expanded Access Program (EAP), was developed to evaluate the effectiveness and safety profile ipilimumab in previously treated patients with advanced melanoma (unresectable or metastatic melanoma). The objective of our retrospective observational study of patients included in this program was to provide data recorded in real-life settings. METHODS: We analysed 89 patients enrolled in Ro-PAP, CA 184-427 (54 men and 35 women) aged between 29 and 89 years...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29120224/is-there-a-role-for-programmed-death-ligand-1-testing-and-immunotherapy-in-colorectal-cancer-with-microsatellite-instability-part-ii-the-challenge-of-programmed-death-ligand-1-testing-and-its-role-in-microsatellite-instability-high-colorectal-cancer
#17
Esmeralda Celia Marginean, Barbara Melosky
CONTEXT: - The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti-programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability-high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability-high CRC...
November 9, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29114542/new-trends-in-antitumor-vaccines-in-melanoma
#18
REVIEW
Marcos Vasquez, Shirley Tenesaca, Pedro Berraondo
Antitumor therapeutic vaccines aim at priming an effector immune response able to recognize and kill tumor cells. Antitumor vaccines are composed of at least two main components: the tumor antigens and the adjuvant. Metastatic advanced melanoma has been a model disease to test novel advances in vaccine design due to the intrinsic immunogenicity of this tumor and the accessibility to melanoma lesions to monitor the immune response. In spite of a large number of clinical trials, clinical benefit remains elusive...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29114389/adoptive-cell-therapy-with-cd4-t-helper-1-cells-and-cd8-cytotoxic-t-cells-enhances-complete-rejection-of-an-established-tumour-leading-to-generation-of-endogenous-memory-responses-to-non-targeted-tumour-epitopes
#19
Kunyu Li, Braeden Donaldson, Vivienne Young, Vernon Ward, Christopher Jackson, Margaret Baird, Sarah Young
The results of adoptive T-cell therapies (ACTs) are very encouraging and show clinical evidence that ACT can provide a cure for patients with metastatic disease. However, various response rates and long-term cancer remission have been observed in different ACT trials. The types of T cells, prior treatment with chemotherapy and co-administration of other immune-target therapies have been found to influence the efficacy of ACT. In this study, we investigate the ability of ACT using CD4(+) T helper 1 (Th1) cells and CD8(+) cytotoxic T lymphocytes (CTLs) to reject the growth of established B16-ovalbumin (OVA) melanoma...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29109964/immunotherapy-as-a-promising-treatment-for-prostate-cancer-a-systematic-review
#20
REVIEW
Marlena Janiczek, Łukasz Szylberg, Anna Kasperska, Adam Kowalewski, Martyna Parol, Paulina Antosik, Barbara Radecka, Andrzej Marszałek
Prostate cancer treatment is currently based on surgical removal, radiotherapy, and hormone therapy. In recent years, another therapeutic method has emerged-immunological treatment. Immunotherapy modulates and strengthens one's immune responses against cancer. Neoplastic cells naturally escape from the control of the immune system, and the main goal of immune therapy is to bring the control back. Satisfying outcomes after treatment of advanced melanoma and lung cancer suggest a great potential of immunotherapy as an approach for other tumors' treatment, especially in patients primarily introduced to palliative care...
2017: Journal of Immunology Research
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