alterations. These include RET rearrangements (cabozantinib, vandetanib), BRAF V600E mutations (vemurafenib, dabrafenib, and dabrafenib + trametinib), MET amplification or exon 14 skipping mutation (crizotinib), and HER2 mutations (trastuzumab and
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Henry G. Kaplan, Steven Rostad, Jeffrey S. Ross, Siraj M. Ali, and Sherri Z. Millis
kinase domain ( BRAF-KD ) duplication. 8 Therapy was discontinued for 1 month, followed by re-treatment with vemurafenib, this time with the addition of trametinib. She had a very good partial response, which lasted for 3 months. On disease progression
Chloe E. Atreya, Claire Greene, Ryan M. McWhirter, Nabia S. Ikram, I. Elaine Allen, Katherine Van Loon, Alan P. Venook, Benjamin M. Yeh, and Spencer C. Behr
-mutated colorectal cancer . J Clin Oncol 2015 ; 33 : 4032 – 4038 . 40. Corcoran RB Atreya CE Falchook GS . Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-mutant colorectal cancer . J Clin Oncol 2015 ; 33 : 4023 – 4031
Cary P. Gross, Craig S. Meyer, Sarika Ogale, Matthew Kent, and William B. Wong
, 2011 (crizotinib); EGFR : May 14, 2013 (erlotinib); ROS1 : March 11, 2016 (crizotinib); PD-L1: October 2, 2015 (pembrolizumab); and BRAF : June 27, 2017 (dabrafenib + trametinib). We identified first-line (1L) therapy occurring within 4 months
Céline Mascaux, Ming-Sound Tsao, and Fred R. Hirsch
rearrangements, which are mainly observed in nonsmokers. 24 For patients with BRAF V600E mutations, the NCCN Guidelines for NSCLC recommend the combination of dabrafenib with trametinib in the first-line setting. 25 Both dabrafenib and vemurafenib as
NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022
Featured Updates to the NCCN Guidelines
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
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
Alan P. Venook, Maria E. Arcila, Al B. Benson III, Donald A. Berry, David Ross Camidge, Robert W. Carlson, Toni K. Choueiri, Valerie Guild, Gregory P. Kalemkerian, Razelle Kurzrock, Christine M. Lovly, Amy E. McKee, Robert J. Morgan, Anthony J. Olszanski, Mary W. Redman, Vered Stearns, Joan McClure, and Marian L. Birkeland
to the development of trametinib, an MEK inhibitor. 45 , 47 , 48 Trametinib is indicated as a single agent and in combination with dabrafenib in patients with unresectable or metastatic melanoma that harbor a BRAF V600E or V600K mutation. It is
Matthew Zibelman and Anthony J. Olszanski
control rates greater than 90%; however, median progression-free survival (PFS) is less than 6 months. 19 - 21 Dual BRAF and MEK inhibition with dabrafenib and trametinib improves RRs to 76% and median PFS to 9.4 months, but few responses prove to be
Daniel G. Coit and Anthony J. Olszanski
progression-free survival was 9.4 months with the combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), versus 5.8 months for dabrafenib monotherapy ( P <.001). 13 The combination is also associated with less skin toxicity, although
