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Margaret von Mehren, John M. Kane III, Richard F. Riedel, Jason K. Sicklick, Seth M. Pollack, Mark Agulnik, Marilyn M. Bui, Janai Carr-Ascher, Edwin Choy, Mary Connelly, Sarah Dry, Kristen N. Ganjoo, Ricardo J. Gonzalez, Ashley Holder, Jade Homsi, Vicki Keedy, Ciara M. Kelly, Edward Kim, David Liebner, Martin McCarter, Sean V. McGarry, Nathan W. Mesko, Christian Meyer, Alberto S. Pappo, Amanda M. Parkes, Ivy A. Petersen, Matthew Poppe, Scott Schuetze, Jacob Shabason, Matthew B. Spraker, Melissa Zimel, Mary Anne Bergman, Hema Sundar, and Lisa E. Hang

specific therapies for GIST with these alterations; however, the presence of these genomic events could be used to identify potential targeted therapy options. For example, combination therapy with dabrafenib and trametinib was recently approved by the FDA

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Robert I Haddad, Lindsay Bischoff, Douglas Ball, Victor Bernet, Erik Blomain, Naifa Lamki Busaidy, Michael Campbell, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Whitney S. Goldner, Theresa Guo, Megan Haymart, Shelby Holt, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Dominick M. Lamonica, Susan Mandel, Stephanie Markovina, Bryan McIver, Christopher D. Raeburn, Rod Rezaee, John A. Ridge, Mara Y. Roth, Randall P. Scheri, Jatin P. Shah, Jennifer A. Sipos, Rebecca Sippel, Cord Sturgeon, Thomas N. Wang, Lori J. Wirth, Richard J. Wong, Michael Yeh, Carly J. Cassara, and Susan Darlow

systemic therapy is indicated, targeted therapy options are preferred. Dabrafenib plus trametinib combination is an option for BRAF V600E mutation-positive tumors, 173 larotrectinib or entrectinib are options for NTRK gene fusion-positive tumors; 174

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Melanoma, Version 2.2013

Featured Updates to the NCCN Guidelines

Daniel G. Coit, Robert Andtbacka, Christopher J. Anker, Christopher K. Bichakjian, William E. Carson III, Adil Daud, Dominick DiMaio, Martin D. Fleming, Valerie Guild, Allan C. Halpern, F. Stephen Hodi Jr., Mark C. Kelley, Nikhil I. Khushalani, Ragini R. Kudchadkar, Julie R. Lange, Anne Lind, Mary C. Martini, Anthony J. Olszanski, Scott K. Pruitt, Merrick I. Ross, Susan M. Swetter, Kenneth K. Tanabe, John A. Thompson, Vijay Trisal, Marshall M. Urist, Nicole McMillian, and Maria Ho

intensity and speed of melanoma research, patients may benefit even more from enrolling in clinical trials of other exciting new treatments, such as the BRAF-inhibitor dabrafenib, MEK-inhibitor trametinib, anti-PD-1 therapy, or combination therapy. 31 – 35

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Bishal Gyawali, Elvira D’Andrea, Jessica M. Franklin, and Aaron S. Kesselheim

phase 1 study . Lancet Oncol 2012 ; 13 : 1011 – 1019 . 10.1016/S1470-2045(12)70344-3 22954507 38. Hauschild A , Grob JJ , Demidov LV , . Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled

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Michelle T. Ashworth and Adil Daud

inhibitor (BRAFi) dabrafenib or vemurafenib beyond disease progression (PD) [abstract] . J Clin Oncol 2013 ; 31 ( Suppl ): Abstract 9062 . 20. Ribas A Hodi FS Callahan M . Hepatotoxicity with combination of vemurafenib and ipilimumab . N Engl

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Henry G. Kaplan

BRAF inhibitors, such as dabrafenib, are now becoming available. 24 The hope is that they will be able to overcome the genetic resistance mechanisms being reported for BRAF itself with regard to vemurafenib. 25 Of particular interest, in light of

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Presenters: Dara L. Aisner and Gregory J. Riely

treatment with the dabrafenib and trametinib regimen. A spectrum of other BRAF mutations are currently under study. For ALK and ROS1 rearrangements, testing looks for a fusion event that leads to aberrant expression and signaling. Biomarker testing

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Louis Burt Nabors, Jana Portnow, Manmeet Ahluwalia, Joachim Baehring, Henry Brem, Steven Brem, Nicholas Butowski, Jian L. Campian, Stephen W. Clark, Andrew J. Fabiano, Peter Forsyth, Jona Hattangadi-Gluth, Matthias Holdhoff, Craig Horbinski, Larry Junck, Thomas Kaley, Priya Kumthekar, Jay S. Loeffler, Maciej M. Mrugala, Seema Nagpal, Manjari Pandey, Ian Parney, Katherine Peters, Vinay K. Puduvalli, Ian Robins, Jason Rockhill, Chad Rusthoven, Nicole Shonka, Dennis C. Shrieve, Lode J. Swinnen, Stephanie Weiss, Patrick Yung Wen, Nicole E. Willmarth, Mary Anne Bergman, and Susan D. Darlow

efficacious in BRAF-mutated low-grade gliomas, particularly PXA, with an ORR of 42.9% (n=7), median PFS of 5.7 months, and median OS not reached. 50 Another phase II trial including 10 patients with low-grade glioma showed that dabrafenib/trametinib was

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Priscilla K. Brastianos, William T. Curry, and Kevin S. Oh

an important role in the treatment of brain metastases from melanoma ( Table 2 ). In a phase II study of the BRAF inhibitor dabrafenib in 172 patients with brain metastases from BRAF -mutant melanoma, response rates were 39% in treatment

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Kevin O’Brien, Rahul Dave, Skand Shekhar, Fady Hannah-Shmouni, Leora E. Comis, Beth I. Solomon, Marcus Chen, William A. Gahl, Edmond FitzGibbon, Bernadette R. Gochuico, and Juvianee I. Estrada-Veras

toxicity due to trametinib and dabrafenib . BMC Ophthalmol 2017 ; 17 : 146 . 28818062 10.1186/s12886-017-0541-0 57. Jeganathan VS , Wirth A , MacManus MP . Ocular risks from orbital and periorbital radiation therapy: a critical review