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Karisa C. Schreck, Andrew Guajardo, Doris D.M. Lin, Charles G. Eberhart, and Stuart A. Grossman

PB Hauschild A Robert C . Improved survival with vemurafenib in melanoma with BRAF V600E mutation . N Engl J Med 2011 ; 364 : 2507 – 2516 . 3. Hauschild A Grob JJ Demidov LV . Dabrafenib in BRAF-mutated metastatic melanoma: a

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William G. Wierda, John C. Byrd, Jeremy S. Abramson, Seema Bhat, Greg Bociek, Danielle Brander, Jennifer Brown, Asher Chanan-Khan, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Jeffrey Lancet, Shuo Ma, Sami Malek, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Andrew D. Zelenetz, Mary A. Dwyer, and Hema Sundar

patients with less-heavily-pretreated HCL that relapsed after cladribine, the ORR and CR rates with rituximab were 80% and 32%, respectively. 51 More recently, tyrosine kinase inhibitors such as vemurafenib (BRAF V600E kinase inhibitor) 52 – 54 and

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Daniel G. Coit, Robert Andtbacka, Christopher J. Anker, Christopher K. Bichakjian, William E. Carson III, Adil Daud, Raza A. Dilawari, Dominick DiMaio, 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, and Marshall M. Urist

drug-related deaths occurred. Approximately 45% of patients with metastatic melanoma harbor an activating mutation of the intracellular signaling kinase, BRAF. Vemurafenib is a specific inhibitor of signaling by mutated BRAF. 116 A randomized phase

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Leonard Saltz

outcome. In addition, no indication has been found for using BRAF inhibitors in CRC. Although BRAF has been identified as an indicator of poor prognosis, the BRAF inhibitor vemurafenib has been shown to not be efficacious against these tumors. 13 The

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Robin K. Kelley, Chloe Atreya, Alan P. Venook, and Phillip G. Febbo

toxicity from the drug being developed. Recent proofs of principle include the demonstration of efficacy of vemurafenib in BRAF V600E mutant melanoma, crizotinib in ALK -rearranged non–small cell lung carcinoma (NSCLC), and EGFR inhibitors in patients

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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

. Identification of a poor-prognosis BRAF-mutant-like population of patients with colon cancer . J Clin Oncol 2012 ; 30 : 1288 – 1295 . 39. Kopetz S Desai J Chan E . Phase II pilot study of vemurafenib in patients with metastatic BRAF

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Annette M. Lim, Graham R. Taylor, Andrew Fellowes, Laird Cameron, Belinda Lee, Rodney J. Hicks, Grant A. McArthur, Christopher Angel, Benjamin Solomon, and Danny Rischin

C . Mutations of the BRAF gene in human cancer . Nature 2002 ; 417 : 949 – 954 . 11. Sosman JA Kim KB Schuchter L . Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib . N Engl J Med 2012 ; 366 : 707 – 714

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Jarred Burkart, Dwight Owen, Manisha H. Shah, Sherif R. Z. Abdel-Misih, Sameek Roychowdhury, Robert Wesolowski, Sigurdis Haraldsdottir, Julie W. Reeser, Eric Samorodnitsky, Amy Smith, and Bhavana Konda

BRAF mutations in CRC has led to mostly disappointing results, 15 , 16 prompting further studies 17 and alternative treatment strategies. In one recently reported phase II study, treatment with vemurafenib in combination with cetuximab and irinotecan

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Karam Khaddour, Michael R. Chicoine, Jiayi Huang, Sonika Dahiya, and George Ansstas

most of these cases showing partial responses based on Response Assessment in Neuro-Oncology (RANO) criteria. 22 Notably, progressive disease was observed in one case report after treatment with vemurafenib alone. 12 Therefore, given the previous

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NCCN Guidelines Insights: Rectal Cancer, Version 6.2020

Featured Updates to the NCCN Guidelines

Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Mustafa A. Arain, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, Andrew Gunn, Sarah Hoffe, Joleen Hubbard, Steven Hunt, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Alyse Johnson-Chilla, and Lisa A. Gurski

, vemurafenib, and cetuximab or panitumumab. This combination was tested in the phase II SWOG S1406 trial of patients with BRAF V600E–mutated mCRC. 35 Ninety-nine patients with BRAF -mutant, RAS wild-type tumors who received 1 or 2 prior regimens were