Melanoma BRAF Inhibitors Review
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Melanoma BRAF Inhibitors Review
Zelboraf (vemurafenib, Roche) and Tafinlar (dabrafenib, GSK) get FDA and EMA approval for advanced metastatic melanoma. Several follow up BRAF inhibitors are in clinical development by rival pharma companies (Novartis, BMS, J&J, Teva) to get a share of expanding melanoma market and improve complete response rates and overcome resistance. Nexavar (sorafenib, Bayer) for for liver (HCC) and renal (RCC) cancer was the first approved and marketed BRAF inhibitor.
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Vemurafenib (PLX 4032, Roche) Melanoma: FDA Review & Approval - un knol de Krishan Maggon

Vemurafenib (PLX 4032, Roche) Melanoma: FDA Review & Approval - un knol de Krishan Maggon | Melanoma BRAF Inhibitors Review | Scoop.it
Only a single new investigation drug has produced a 81% response rate and extended overall survival by 7 months (range 2-18...
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Radiation therapy for melanoma skin cancer

Radiation therapy for melanoma skin cancer | Melanoma BRAF Inhibitors Review | Scoop.it
American Cancer Society: Radiation therapy is a treatment that uses high-energy rays to kill cancer cells or shrink tumors. Learn about radiation therapy for melanoma skin cancer here.
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Decoding Cancer

Decoding Cancer | Melanoma BRAF Inhibitors Review | Scoop.it

Can individualized cancer vaccines help us build custom cancer treatments?


The first step after diagnosis is often to analyze the tumor for genetic mutations that can help identify the most effective targeted treatments. People who find a match can sometimes live free of cancer for many years. But many people still don’t find a match, and even the most targeted therapies work differently across groups of people with similar genetic mutations. So after producing some encouraging pre-clinical results, Genentech has entered into an agreement with BioNTech, an expert in next-generation immunotherapies, to develop a cancer vaccine that would be truly personalized.

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Metastatic melanoma and immunotherapy

Metastatic melanoma and immunotherapy | Melanoma BRAF Inhibitors Review | Scoop.it
Abstract Harnessing the immune system to attack cancer cells has represented a holy grail for greater than 100 years. While prospects of tumor-selective durable immune based therapies have provided small clinical signals for many decades, recent years have demonstrated a virtual explosion in progress. Melanoma has led the field of cancers in which immunotherapy has produced major clinical inroads. The most significant and impactful immunotherapies for melanoma utilize immune checkpoint inhibition to stimulate T cell mediated tumor killing. The major targets of checkpoint blockade have thus far been CTLA4 and PD1, two key receptors for central and peripheral immune tolerance. This review discusses current understanding of how these checkpoint blockade therapeutics have led to major clinical responses in patients with advanced melanoma. It is likely that we are poised to see significantly greater anti-cancer immunotherapy efficacy, both in improving response rates and durability for melanoma, and for other less immunogenic malignancies. Keywords melanoma; immunotherapy; T cell; checkpoint; vitiligo
Krishan Maggon 's insight:
Clinical Immunology Available online 16 July 2016 
http://dx.doi.org/10.1016/j.clim.2016.07.006

 In Press, Accepted Manuscript

Benjamin Herzberg, , David E. Fisher
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MD Anderson IDs gene mutations responsible for melanoma drug resistance | FierceBiotech

MD Anderson IDs gene mutations responsible for melanoma drug resistance | FierceBiotech | Melanoma BRAF Inhibitors Review | Scoop.it
MD Anderson scientists have pinpointed how melanoma tumors resist the cancer drug ipilimumab: genetic mutations in an immune pathway.
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COLUMBUS Phase 3 Study of Encorafenib plus Binimetinib For BRAF-Mutant Melanoma Met Primary Endpoint. Array BioPharma/Pierre Fabre

COLUMBUS Phase 3 Study of Encorafenib plus Binimetinib For BRAF-Mutant Melanoma Met Primary Endpoint. Array BioPharma/Pierre Fabre | Melanoma BRAF Inhibitors Review | Scoop.it
BOULDER, Colo., Sept. 26, 2016 /PRNewswire/ -- Array BioPharma (Nasdaq: ARRY) and Pierre Fabre today jointly announced top-line results from Part 1 of the Phase 3 COLUMBUS (Combined LGX818 Used with MEK162 in BRAF Mutant Unresectable Skin Cancer) study evaluating LGX818 (encorafenib), a BRAF inhibitor, and MEK162 (binimetinib), a MEK inhibitor, in patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The study met its primary endpoint, significantly improving progression free survival (PFS) compared with vemurafenib, a BRAF inhibitor, alone.

In the analysis of the primary endpoint, the median PFS for patients treated with the combination of encorafenib plus binimetinib ("combination") was 14.9 months versus 7.3 months for patients treated with vemurafenib; HR (0.54), [95% CI 0.41-0.71], p<0.001. The combination was generally well-tolerated and reported adverse events were overall consistent with previous combination encorafenib plus binimetinib clinical trial results in BRAF-mutant melanoma patients.
Krishan Maggon 's insight:
About Binimetinib & Encorafenib 

 MEK and BRAF are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as melanoma, colorectal and thyroid cancers. Binimetinib is a late-stage small molecule MEK inhibitor and encorafenib is a late-stage small molecule BRAF inhibitor, both of which target key enzymes in this pathway. Binimetinib and encorafenib are being studied in clinical trials in advanced cancer patients, including the recently initiated Phase 3 BEACON CRC trial that will study encorafenib in combination with cetuximab with or without binimetinib in patients with BRAF V600E-mutant colorectal cancer. 

Array submitted a New Drug Application (NDA) for binimetinib in NRAS-mutant melanoma to the FDA at the end of June 2016. The FDA accepted the NDA with a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2017. Array BioPharma retains exclusive rights to binimetinib and encorafenib in key markets including the U.S. and Japan.
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Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients

Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients | Melanoma BRAF Inhibitors Review | Scoop.it
Nature Medicine | doi:10.1038/nm.4051

We show that neoantigen-specific T cells and gene-engineered lymphocytes expressing neoantigen-specific T cell receptors (TCRs) isolated from peripheral blood recognized autologous tumors. Notably, the tumor-antigen specificities and TCR repertoires of the circulating and tumor-infiltrating CD8+PD-1+ cells appeared similar, implying that the circulating CD8+PD-1+ lymphocytes could provide a window into the tumor-resident antitumor lymphocytes. Thus, expression of PD-1 identifies a diverse and patient-specific antitumor T cell response in peripheral blood, providing a novel noninvasive strategy to develop personalized therapies using neoantigen-reactive lymphocytes or TCRs to treat cancer.
Krishan Maggon 's insight:
Alena Gros, Maria R Parkhurst, Eric Tran, Anna Pasetto, Paul F Robbins, Sadia Ilyas, Todd D Prickett, Jared J Gartner, Jessica S Crystal, Ilana M Roberts, Kasia Trebska-McGowan, John R Wunderlich, James C Yang & Steven A Rosenberg

Nature Medicine  VOLUME 22 | NUMBER 4 | APRIL 2016
published online 22 February 2016; doi:10.1038/nm.4051
npg© 2016 Nature America, Inc. 
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Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects

Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects | Melanoma BRAF Inhibitors Review | Scoop.it
Local and systemic treatments for advanced or metastatic cancer are rarely curative. Innate and/or acquired resistance can reduce therapy responsiveness, with studies highlighting the contribution of therapy-induced physiological changes in host tissues and cells that reduce the antitumour effects of therapy. These unwanted host effects can promote tumour-cell repopulation and malignant aggressiveness. In this Review, the author discusses ways to suppress these host-response effects as a possible new approach to improving local and systemic cancer therapies.
Krishan Maggon 's insight:
Yuval Shaked 
Nature Reviews Clinical Oncology 13, 611–626 (2016) doi:10.1038/nrclinonc.2016.57 
Published online 26 April 2016 Article tools
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DOT1L promotes angiogenesis through cooperative regulation of VEGFR2 with ETS-1 | Duan | Oncotarget

DOT1L promotes angiogenesis through cooperative regulation of VEGFR2 with ETS-1 | Duan | Oncotarget | Melanoma BRAF Inhibitors Review | Scoop.it
DOT1L promotes angiogenesis through cooperative regulation of VEGFR2 with ETS-1
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Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial | Melanoma BRAF Inhibitors Review | Scoop.it
Findings Between Sept 16, 2013, and Feb 6, 2014, we screened 179 patients and enrolled 142, randomly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone. In each treatment group, one patient no longer met the study criteria following randomisation and thus did not receive study drug. At a median follow-up of 24·5 months (IQR 9·1–25·7), 2-year overall survival was 63·8% (95% CI 53·3–72·6) for those assigned to nivolumab plus ipilimumab and 53·6% (95% CI 38·1–66·8) for those assigned to ipilimumab alone; median overall survival had not been reached in either group (hazard ratio 0·74, 95% CI 0·43–1·26; p=0·26). Treatment-related grade 3–4 adverse events were reported in 51 (54%) of 94 patients who received nivolumab plus ipilimumab compared with nine (20%) of 46 patients who received ipilimumab alone. The most common treatment-related grade 3–4 adverse events were colitis (12 [13%] of 94 patients) and increased alanine aminotransferase (ten [11%]) in the combination group and diarrhoea (five [11%] of 46 patients) and hypophysitis (two [4%]) in the ipilimumab alone group. Serious grade 3–4 treatment-related adverse events were reported in 34 (36%) of 94 patients who received nivolumab plus ipilimumab (including colitis in ten [11%] of 94 patients, and diarrhoea in five [5%]) compared with four (9%) of 46 patients who received ipilimumab alone (including diarrhoea in two [4%] of 46 patients, colitis in one [2%], and hypophysitis in one [2%]). No new types of treatment-related adverse events or treatment-related deaths occurred in this updated analysis. 

 Interpretation Although follow-up of the patients in this study is ongoing, the results of this analysis suggest that the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma. The results suggest encouraging survival outcomes with immunotherapy in this population of patients. 

 Funding Bristol-Myers Squibb.
Krishan Maggon 's insight:
Dr F Stephen Hodi, MDcorrespondencePress enter key for correspondence informationemailPress enter key to Email the author, Prof Jason Chesney, MD, Anna C Pavlick, MD, Prof Caroline Robert, MD, Kenneth F Grossmann, MD, David F McDermott, MD, Gerald P Linette, MD, Prof Nicolas Meyer, MD, Jeffrey K Giguere, MD, Prof Sanjiv S Agarwala, MD, Montaser Shaheen, MD, Prof Marc S Ernstoff, MD, David R Minor, MD, April K Salama, MD, Matthew H Taylor, MD, Patrick A Ott, MD, Christine Horak, PhD, Paul Gagnier, MD, Joel Jiang, PhD, Prof Jedd D Wolchok, MD†, Michael A Postow, MD† †Contributed equally Published Online: 08 September 2016 Article has an altmetric score of 22 DOI: http://dx.doi.org/10.1016/S1470-2045(16)30366-7
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T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells

T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells | Melanoma BRAF Inhibitors Review | Scoop.it
Summary Effective cancer immunotherapy requires overcoming immunosuppressive tumor microenvironments. We found that local nitric oxide (NO) production by tumor-infiltrating myeloid cells is important for adoptively transferred CD8+ cytotoxic T cells to destroy tumors. These myeloid cells are phenotypically similar to inducible nitric oxide synthase (NOS2)- and tumor necrosis factor (TNF)-producing dendritic cells (DC), or Tip-DCs. Depletion of immunosuppressive, colony stimulating factor 1 receptor (CSF-1R)-dependent arginase 1+ myeloid cells enhanced NO-dependent tumor killing. Tumor elimination via NOS2 required the CD40-CD40L pathway. We also uncovered a strong correlation between survival of colorectal cancer patients and NOS2, CD40, and TNF expression in their tumors. Our results identify a network of pro-tumor factors that can be targeted to boost cancer immunotherapies.
Krishan Maggon 's insight:
Ilaria Marigo11,correspondencePress enter key for correspondence informationemailPress enter key to Email the author, Serena Zilio, Giacomo Desantis, Bernhard Mlecnik, Andrielly H.R. Agnellini, Stefano Ugel, Maria Stella Sasso, Joseph E. Qualls, Franz Kratochvill, Paola Zanovello, Barbara Molon10, Carola H. Ries, Valeria Runza, Sabine Hoves, Amélie M. Bilocq, Gabriela Bindea, Emilia M.C. Mazza, Silvio Bicciato, Jérôme Galon, Peter J. MurraycorrespondencePress enter key for correspondence informationemailPress enter key to Email the author, Vincenzo BrontecorrespondencePress enter key for correspondence informationemailPress enter key to Email the author 10Present address: Venetian Institute of Molecular Medicine (VIMM), 35129 Padova, Italy 11Lead Contact DOI: http://dx.doi.org/10.1016/j.ccell.2016.08.004
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Nature Reviews Clinical Oncology - Table of Contents alert Volume 13 Issue 10

Nature Reviews Clinical Oncology - Table of Contents alert Volume 13 Issue 10 | Melanoma BRAF Inhibitors Review | Scoop.it
If you are unable to see the message below, click here to view . Advertisement
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Delivering the promise of immunotherapy for melanoma

Delivering the promise of immunotherapy for melanoma | Melanoma BRAF Inhibitors Review | Scoop.it
At the European Society for Medical Oncology (ESMO) Asia 2015 Congress, held in Singapore from 18 December to 21 December 2015, Peter Hersey, MD, PhD, from the Melanoma Institute Australia, Sydney, Australia, discusses the opportunities and...
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BMS Stays the Course on Opdivo as Rivals Gain Steam | Insight & Intelligence™ | GEN

BMS Stays the Course on Opdivo as Rivals Gain Steam | Insight & Intelligence™ | GEN | Melanoma BRAF Inhibitors Review | Scoop.it
NMerck, AstraZeneca, and Pfizer Hunt for an advantage for non-small-cell lung cancer (NSCLC).
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Tipping the Scales with OX40 at Genentech

Tipping the Scales with OX40 at Genentech | Melanoma BRAF Inhibitors Review | Scoop.it

With OX40, we may have found a way to activate the body’s immune system to fight cancer.


To target this specific process. When T cells are presented with antigens, a protein called OX40 on the cell’s surface helps enhance T cell activation. By using an immunotherapy called anti-OX40—which counter to its name is an antibody that actually binds to and turns on OX40—we can increase immune system activation.

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(Neo)adjuvant systemic therapy for melanoma

(Neo)adjuvant systemic therapy for melanoma | Melanoma BRAF Inhibitors Review | Scoop.it
Abstract Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas. 

 Keywords Cutaneous melanoma; High risk melanoma; Melanoma; Adjuvant; Neoadjuvant; Immunotherapy; Anti CTLA-4; Ipilimumab; BRAF inhibitor; Vemurafenib; Dabrafenib; MEK inhibitor; Trametinib; Cobimetinib; Anti PD1; T-VEC; Tamilogene Laherparepvec;
Krishan Maggon 's insight:
European Journal of Surgical Oncology (EJSO) Available online 11 July 2016 In Press, Corrected Proof

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Cancer killers: C dots show ability to induce cell death in tumors - Technology Org

Cancer killers: C dots show ability to induce cell death in tumors - Technology Org | Melanoma BRAF Inhibitors Review | Scoop.it
Nanoparticles known as Cornell dots, or C dots, have shown great promise as a therapeutic tool in the
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Ratio of Certain Immune Cells to Tumor Burden Correlated With Outcome for Pembrolizumab-Treated Patients With Melanoma : Oncology Times

Ratio of Certain Immune Cells to Tumor Burden Correlated With Outcome for Pembrolizumab-Treated Patients With Melanoma : Oncology Times | Melanoma BRAF Inhibitors Review | Scoop.it
An abstract is unavailable.
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Iron nanoparticles make immune cells attack cancer - Scienmag

Iron nanoparticles make immune cells attack cancer - Scienmag | Melanoma BRAF Inhibitors Review | Scoop.it
Iron nanoparticles can activate the immune system to attack cancer cells, according to a study led by researchers at the Stanford University School of Medicine.
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Targeting the cancer epigenome for therapy

Targeting the cancer epigenome for therapy | Melanoma BRAF Inhibitors Review | Scoop.it
Recent drug discovery efforts in cancer have focused on epigenetic marks, such as DNA methylation and histone modifications. The authors discuss existing therapeutics that target the cancer epigenome, the role of epigenetic marks as biomarkers of drug response and emerging strategies that combine epigenetic drugs with other cancer therapies.
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OppenheimerFundsVoice: Immunotherapy: A Game-Changer For Cancer Treatment?

OppenheimerFundsVoice: Immunotherapy: A Game-Changer For Cancer Treatment? | Melanoma BRAF Inhibitors Review | Scoop.it
He was only 44 years old, and the drug Kevin Williamson was taking to fight his bladder cancer wasn’t working.
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Altered metabolite levels in cancer: implications for tumour biology and cancer therapy

Altered metabolite levels in cancer: implications for tumour biology and cancer therapy | Melanoma BRAF Inhibitors Review | Scoop.it
Altered cell metabolism is a characteristic feature of many cancers. Aside from well-described changes in nutrient consumption and waste excretion, altered cancer cell metabolism also results in changes to intracellular metabolite concentrations. Increased levels of metabolites that result directly from genetic mutations and cancer-associated modifications in protein expression can promote cancer initiation and progression. Changes in the levels of specific metabolites, such as 2-hydroxyglutarate, fumarate, succinate, aspartate and reactive oxygen species, can result in altered cell signalling, enzyme activity and/or metabolic flux. In this Review, we discuss the mechanisms that lead to changes in metabolite concentrations in cancer cells, the consequences of these changes for the cells and how they might be exploited to improve cancer therapy.
Krishan Maggon 's insight:
Lucas B. Sullivan, Dan Y. Gui & Matthew G. Vander Heiden 

Nature Reviews Cancer (2016) doi:10.1038/nrc.2016.85 Published online 23 September 2016
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Metastatic Cancer

Metastatic Cancer | Melanoma BRAF Inhibitors Review | Scoop.it
Defines metastatic cancer and describes the process of metastasis. Includes information about possible symptoms, common sites where cancer spreads, and how to find out about treatment options.
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LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells

LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells | Melanoma BRAF Inhibitors Review | Scoop.it
Highlights 

•Human melanoma metastases exhibit a “Warburg phenotype” with high lactic acid levels 
•LDHA-associated lactic acid production and acidification lead to immune evasion •Lactic acid and acidification diminish NFAT levels and T and NK cell activation 
•LDHA expression in melanoma patients correlates with survival and T cell activity
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Almut Brand, Katrin Singer, Gudrun E. Koehl, Marlene Kolitzus, Gabriele Schoenhammer, Annette Thiel, Carina Matos, Christina Bruss, Sebastian Klobuch, Katrin Peter, Michael Kastenberger, Christian Bogdan, Ulrike Schleicher, Andreas Mackensen, Evelyn Ullrich, Stefan Fichtner-Feigl, Rebecca Kesselring, Matthias Mack, Uwe Ritter, Maximilian Schmid, Christian Blank, Katja Dettmer, Peter J. Oefner, Petra Hoffmann, Stefan Walenta, Edward K. Geissler, Jacques Pouyssegur, Andreas Villunger, André Steven, Barbara Seliger, Stephan Schreml, Sebastian Haferkamp, Elisabeth Kohl, Sigrid Karrer, Mark Berneburg, Wolfgang Herr, Wolfgang Mueller-Klieser, Kathrin Renner, Marina Kreutz18,correspondencePress enter key for correspondence informationemailPress enter key to Email the author 18Lead Contact Publication stage: In Press Corrected Proof DOI: http://dx.doi.org/10.1016/j.cmet.2016.08.011 showArticle Info
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Dying tumour cells release intracellular ions in a last-ditch attempt to block the immune system. ecancer - News

Dying tumour cells release intracellular ions in a last-ditch attempt to block the immune system. ecancer - News | Melanoma BRAF Inhibitors Review | Scoop.it
Dying tumour cells release intracellular ions in a last-ditch attempt to block the immune system. ecancer - News https://t.co/0rrPFRSuDe
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Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience | TJ

Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience | TJ | Melanoma BRAF Inhibitors Review | Scoop.it
RT @elenacolombo99: #Dabrafenib and #trametinib in metastatic #melanoma: the #INTMilan experience
https://t.co/OR6v4y5TRz

Abstract 

Purpose Combination therapy with dabrafenib and trametinib is safer and more effective than BRAF inhibitor-based monotherapy for metastatic melanoma. 

Methods We retrospectively analyzed BRAF-mutated metastatic melanoma patients treated at our institution with daily oral dabrafenib 300 mg and trametinib 2 mg from November 2013 to April 2016. This clinical record included both untreated and previously treated stage IV melanomas. Physical examination and laboratory examinations were performed monthly and disease re-evaluations were performed every 3 months. 

 Results A total of 48 patients (24 male, 24 female) with BRAF-mutated metastatic melanoma received dabrafenib and trametinib; median age was 48 years (range 23-75). Median follow-up was 362.5 days (range 72-879). Best overall response rate consisted of 6.2% (3 patients) complete response, 64.6% (31) partial response, and 25% (12) stable disease; median time to best response was 11 weeks (range 5.7-125.5). Progression of disease was seen in 19 patients (39.6%), with median time to progression (TTP) of 26 weeks (range 8-54). A total of 15 patients (31.2%) died due to progression of disease. Median progression-free survival and median overall survival were not reached. To date, 30 patients (62.5%) are still under treatment. A total of 27 (56.2%) patients had at least one adverse event (AE); grade 3-4 AEs were seen in 4 cases (8.3%). The main toxicities were fever (25%), skin rash (14.6%), arthralgias (10.4%), and aspartate aminotransferase/alanine aminotransferase increase (8.3%). Treatment dose was reduced in 7 subjects (14.6%), with only one case of discontinuation due to AE. 

 Conclusions Our data, using combined targeted therapy, are in line with the scientific literature in terms of both safety and effectiveness in a real-life setting.
Krishan Maggon 's insight:
Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience Post author correction 

Article Type: ORIGINAL RESEARCH ARTICLE 
Article Subject: Melanoma and sarcoma 
DOI:10.5301/tj.5000539 
Authors Stefano Cavalieri, Lorenza Di Guardo, Carolina Cimminiello, Aldo Bono, Elena Tolomio, Anna Colombetti, Barbara Valeri, Giuseppe Di Tolla, Filippo de Braud, Michele Del Vecchio
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