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https://www.readbyqxmd.com/read/28628251/a-network-meta-analysis-of-short-and-long-term-efficacy-of-targeted-therapy-with-single-or-double-drug-regimens-in-the-treatment-of-stage-iii-iv-malignant-melanoma-based-on-16-randomized-controlled-trials
#1
Ting Xie, Chun-Yu Huang, Xu Kang, Jia-Sheng Luo, Xiao-Min Qin, Feng Han
For the treatment of stage III/IV malignant melanoma (MM), a network meta-analysis (NMA) was conducted to compare the short and long-term efficacy of targeted therapy with single or double-drug regimens. All conducted randomized controlled trials (RCTs) searched from PubMed and Cochrane Library were included in the study for direct and indirect comparison for MM. The odds ratio (OR) and surface under the cumulative ranking curves (SUCRA) value of the targeted therapy with single or double-drug regimens for treatment of stage III/IV MM were also analyzed...
June 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28626033/dabrafenib-plus-trametinib-achieves-overall-and-intracranial-responses
#2
(no author information available yet)
Dabrafenib plus trametinib achieves intracranial responses in BRAF-mutant melanoma brain metastases.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28614138/acute-exudative-paraneoplastic-polymorphous-vitelliform-maculopathy-during-vemurafenib-and-pembrolizumab-treatment-for-metastatic-melanoma
#3
Harpal S Sandhu, Anton M Kolomeyer, Marisa K Lau, Carol L Shields, Lynn M Schuchter, Charles W Nichols, Tomas S Aleman
PURPOSE: To describe a patient with BRAF mutation-positive cutaneous melanoma who developed acute exudative polymorphous vitelliform maculopathy during vemurafenib and pembrolizumab treatment for metastatic melanoma. METHODS: Retrospective case report documented with wide-field fundus imaging, spectral domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: A 55-year-old woman with bilateral ductal breast carcinoma and BRAF mutation-positive metastatic cutaneous melanoma complained of bilateral blurred vision within 5 days of starting vemurafenib (BRAF inhibitor)...
June 13, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28611627/panniculitis-associated-with-mek-inhibitor-therapy-an-uncommon-adverse-effect
#4
Miruna Negulescu, Florian Deilhes, Vincent Sibaud, Emilie Tournier, Laurence Lamant, Serge Boulinguez, Nicolas Meyer
The combination of MEK inhibitor (cobimetinib, trametinib) and BRAF inhibitor (vemurafenib, dabrafenib) is now the first-line treatment in patients with BRAF V600-mutated metastatic melanoma. This association reduces cutaneous adverse events induced by BRAF inhibitors alone, including photosensitivity, hand-foot syndrome, hyperkeratosis, alopecia, skin papillomas, keratoacanthomas, and squamous-cell carcinomas. While panniculitis has exceptionally been reported with BRAF inhibitors, this rare side effect has never been described with the use of MEK inhibitors...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28608286/survival-of-melanoma-patients-treated-with-novel-drugs-retrospective-analysis-of-real-world-data
#5
Marta Polkowska, Paweł Ekk-Cierniakowski, Edyta Czepielewska, Wojciech Wysoczański, Wojciech Matusewicz, Małgorzata Kozłowska-Wojciechowska
PURPOSE: Recently, several new drugs have been licensed for advanced melanoma therapy, significantly changing the therapeutic landscape. Ipilimumab and vemurafenib were the first drugs that demonstrated a survival benefit over the long-standing standard therapy with dacarbazine. However, the comparative efficacy of these novel drugs has not been properly assessed yet. PATIENTS AND METHODS: We conducted a retrospective analysis of all the Polish population treated between January 2012 and October 2016 with one of the following agents: ipilimumab (IPI), vemurafenib (VEM), dabrafenib (DAB), and classic chemotherapy (CTH)...
June 12, 2017: Journal of Cancer Research and Clinical 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
#6
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/28567600/dabrafenib-therapy-in-30-patients-with-melanoma-metastatic-to-the-brain-a-single-centre-controlled-retrospective-study-in-hungary
#7
Eszter Gorka, Dániel Fabó, András Gézsi, Kata Czirbesz, Imre Fedorcsák, Gabriella Liszkay
Dabrafenib is a potent BRAF inhibitor, which showed intracranial tumor activity. The purpose of our retrospective analysis was to evaluate the efficacy of dabrafenib for patients with melanoma brain metastasis (BM). We studied 30 BRAF mutant melanoma patients with BM, who received dabrafenib after local control of the brain between 2014 and 2017. Eastern Cooperative Oncology Group Performance Status (ECOG) was 0-2. The control arm consisted of 204 melanoma patients from our institutional melanoma database with BM and ECOG 0-2 treated with local therapies and/or chemotherapy, between 2003 and 2015...
June 1, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28557366/radiosensitization-by-braf-inhibitors
#8
Sophia Boyoung Strobel, Sylvie Pätzold, Lisa Zimmer, Alexandra Jensen, Alexander Enk, Jessica Cecile Hassel
BACKGROUND: Increased skin toxicity during combination therapy with a BRAF inhibitor and radiation therapy has recently been reported. MATERIAL AND METHODS: We present seven melanoma patients with non-resectable stage III or IV disease and concomitant treatment with a BRAF inhibitor and radiation therapy. RESULTS: In all patients, combination therapy yielded a good local response. Only two patients, both on vemurafenib, showed severe radiation dermatitis (CTCAE grade 3/4) after one and two weeks, respectively, resulting in interruption of BRAF inhibitor treatment...
May 30, 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28553668/the-clinical-spectrum-of-erdheim-chester-disease-an-observational-cohort-study
#9
Juvianee I Estrada-Veras, Kevin J O'Brien, Louisa C Boyd, Rahul H Dave, Benjamin Durham, Liqiang Xi, Ashkan A Malayeri, Marcus Y Chen, Pamela J Gardner, Jhonell R Alvarado-Enriquez, Nikeith Shah, Omar Abdel-Wahab, Bernadette R Gochuico, Mark Raffeld, Elaine S Jaffe, William A Gahl
Erdheim-Chester Disease (ECD) is a rare, potentially fatal, multi-organ myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a-, and frequently S100-. The purpose of this report is to describe the clinical and molecular variability of ECD. Sixty consecutive ECD patients (45 males, 15 females) were prospectively evaluated at the NIH Clinical Center between 2011 and 2015. Comprehensive imaging and laboratory studies were performed, and tissues were examined for BRAF V600E and MAPK pathway mutations...
February 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#10
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28537004/mek-inhibitors-in-the-treatment-of-metastatic-melanoma-and-solid-tumors
#11
REVIEW
Antonio M Grimaldi, Ester Simeone, Lucia Festino, Vito Vanella, Martina Strudel, Paolo A Ascierto
The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines...
May 23, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28536078/akt-is-critically-involved-in-the-antagonism-of-braf-inhibitor-sorafenib-against-dabrafenib-in-colorectal-cancer-cells-harboring-both-wild-type-and-mutant-v600e-braf-genes
#12
Hongbin Wang, Haitian Quan, Liguang Lou
BRAF, one of the key factors in mitogen-activated protein kinase (MAPK) signaling pathway, plays an important role in cell functions including growth and proliferation. Inhibition of BRAF represents a promising antitumor strategy. Dabrafenib, a type I inhibitor of BRAF interrupting RAF/MEK interaction, has been approved by FDA as a single agent or combined with MEK inhibitor trametinib for the treatment of patients with BRAF V600E mutation-positive advanced melanoma. In the present study, we investigated the feasibility of combined treatment with dabrafenib and sorafenib, type I and type II BRAF inhibitor respectively, on colorectal cancer cells with BRAF V600E mutation...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526719/management-of-treatment-related-adverse-events-with-agents-targeting-the-mapk-pathway-in-patients-with-metastatic-melanoma
#13
Adil Daud, Katy Tsai
Tremendous progress has been made in the clinical landscape of advanced-stage BRAF V600-mutant melanoma treatment over the past 5 years. Targeted therapies that inhibit specific steps of the mitogen-activated protein kinase pathway have been shown to provide significant overall treatment benefit in patients with this difficult-to-treat disease. Combination therapy with BRAF and MEK inhibitors (dabrafenib plus trametinib or vemurafenib plus cobimetinib, respectively) has become standard of care. These agents are administered until disease progression or unacceptable toxicity occurs; thus, some patients may remain on maintenance therapy for an extended period of time, while toxicities may result in early discontinuation in other patients...
May 18, 2017: Oncologist
https://www.readbyqxmd.com/read/28520456/development-and-validation-of-a-micellar-liquid-chromatographic-method-to-determine-three-antitumorals-in-plasma
#14
Josep Esteve Romero, Jaume Albiol Chiva, Juan Peris-Vicente, Enrique Ochoa-Aranda
AIM: A micellar liquid chromatographic method to determine several anticancer drugs (pazopanib, dabrafenib and regorafenib) in plasma was developed and validated by the guidelines of the EMA. EXPERIMENTAL: Plasma samples were directly injected, after a 1/5-dilution in a micellar solution. The drugs were resolved in <18 min using a C18 column. The mobile phase was an aqueous solution of 0.12 M SDS - 2% 1-pentanol, buffered at pH 7. The detection was performed by absorbance at 260 nm...
May 18, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28500236/identification-of-the-serine-biosynthesis-pathway-as-a-critical-component-of-braf-inhibitor-resistance-of-melanoma-pancreatic-and-non-small-cell-lung-cancer-cells
#15
Kayleigh C Ross, Andrew J Andrews, Christopher D Marion, Timothy J Yen, Vikram Bhattacharjee
Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors (BRAFis). In this study, we identified serine biosynthesis as a critical mechanism of resistance. Proteomic assays revealed differential protein expression of serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi) treatment in sensitive versus acquired resistant melanoma cells. Ablation of PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting the folate cycle, directly downstream of serine synthesis, with methotrexate also displayed similar sensitization...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28480077/combined-dabrafenib-and-trametinib-treatment-in-a-case-of-chemotherapy-refractory-extrahepatic-braf-v600e-mutant-cholangiocarcinoma-dramatic-clinical-and-radiological-response-with-a-confusing-synchronic-new-liver-lesion
#16
Judit Kocsis, Anita Árokszállási, Csilla András, Ingrid Balogh, Edit Béres, Júlia Déri, István Peták, Levente Jánváry, Zsolt Horváth
Since the prognosis of advanced cholangiocarcinoma (CCA) remains poor with traditional chemotherapy, attention has shifted to molecularly targeted agents. Results of available clinical studies reveal little or no benefit of using targeted agents in advanced CCA. Limitations of these trials could be the lack of comprehensive molecular and genetic characterization of CCA samples in order to identify potential drug targets. Here we report a case of a 59-year-old female with chemotherapy-refractor, metastatic extrahepatic cholangiocarcinoma (EHCCA)...
April 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28475671/dabrafenib-plus-trametinib-versus-dabrafenib-monotherapy-in-patients-with-metastatic-braf-v600e-k-mutant-melanoma-long-term-survival-and-safety-analysis-of-a-phase-3-study
#17
G V Long, K T Flaherty, D Stroyakovskiy, H Gogas, E Levchenko, F de Braud, J Larkin, C Garbe, T Jouary, A Hauschild, V Chiarion-Sileni, C Lebbe, M Mandalà, M Millward, A Arance, I Bondarenko, J B A G Haanen, J Hansson, J Utikal, V Ferraresi, P Mohr, V Probachai, D Schadendorf, P Nathan, C Robert, A Ribas, M A Davies, S R Lane, J J Legos, B Mookerjee, J-J Grob
Background: Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods: This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma...
May 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28429064/simple-and-cost-effective-liquid-chromatography-mass-spectrometry-method-to-measure-dabrafenib-quantitatively-and-six-metabolites-semi-quantitatively-in-human-plasma
#18
Svante Vikingsson, Jan-Olof Dahlberg, Johan Hansson, Veronica Höiom, Henrik Gréen
Dabrafenib is an inhibitor of BRAF V600E used for treating metastatic melanoma but a majority of patients experience adverse effects. Methods to measure the levels of dabrafenib and major metabolites during treatment are needed to allow development of individualized dosing strategies to reduce the burden of such adverse events. In this study, an LC-MS/MS method capable of measuring dabrafenib quantitatively and six metabolites semi-quantitatively is presented. The method is fully validated with regard to dabrafenib in human plasma in the range 5-5000 ng/mL...
June 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28425764/braf-v600e-mutant-papillary-craniopharyngioma-dramatically-responds-to-combination-braf-and-mek-inhibitors
#19
Ashley Roque, Yazmin Odia
We present a patient with BRAF-V600E mutant papillary craniopharyngioma successfully treated with combination BRAF (dabrafenib 150 mg twice daily) and MEK (trametinib 2 mg daily) inhibitors after her unresectable tumor proved refractory to radiation. Serial brain MRIs and PET revealed marked tumor reduction with gradual neurological improvement and permanent panhypopituitarism.
April 2017: CNS Oncology
https://www.readbyqxmd.com/read/28423638/her-inhibitor-promotes-braf-mek-inhibitor-induced-redifferentiation-in-papillary-thyroid-cancer-harboring-brafv600e
#20
Lingxiao Cheng, Yuchen Jin, Min Liu, Maomei Ruan, Libo Chen
Redifferentiation therapy with BRAF/MEK inhibitors to facilitate treatment with radioiodine represents a good choice for radioiodine-refractory differentiated thyroid carcinoma, but recent initial clinical outcomes were modest. MAPK rebound caused by BRAF/MEK inhibitors-induced activation of HER2/HER3 is a resistance mechanism, and combination with HER inhibitor to prevent MAPK rebound may sensitize BRAFV600E-mutant thyroid cancer cells to redifferentiation therapy. To evaluate if inhibiting both BRAF/MEK and HER can produce stronger redifferetiation effect, we tested the effects of BRAF/MEK inhibitor dabrafenib/selumetinib alone or in combination with HER inhibitor lapatinib on the expression and function of iodine- and glucose-handling genes in BRAFV600E-positive BCPAP and K1 cells, using BHP 2-7 cells harboring RET/PTC1 rearrangement as control...
March 21, 2017: Oncotarget
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