dramatic improvement in relapse-free survival versus placebo. 5 “It’s debated whether BRAF/MEK inhibition or anti–PD-1 is a better treatment option in the adjuvant setting, but it’s certainly clinically indicated to test for BRAF mutations in the stage
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Presented by: Douglas B. Johnson, Susan M. Swetter, April K.S. Salama, and Evan Wuthrick
Christina Rybak and Michael J. Hall
. BRAF encodes a kinase involved in response to growth signals. BRAF mutation leads to constitutive activity of the kinase. 33 BRAF V600E accounts for approximately 90% of all activating BRAF mutations. 33 Clinically, most CRCs with dMMR from
Al B. Benson III, Alan P. Venook, Mahmoud M. Al-Hawary, Lynette Cederquist, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Paul F. Engstrom, Ignacio Garrido-Laguna, Jean L. Grem, Axel Grothey, Howard S. Hochster, Sarah Hoffe, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Evan Wuthrick, Kristina M. Gregory, and Deborah A. Freedman-Cass
there are not enough data from IDEA to draw any conclusions for patients with rectal or stage II colon cancer. Treatment of RAS Wild-Type/ BRAF Mutation–Positive Metastatic CRC In the 2017 version of the NCCN Guidelines, patients with
Karolina Kata, Juan C. Rodriguez-Quintero, Octavio D. Arevalo, Jackie J. Zhang, Meenakshi Bidwai Bhattacharjee, Cornelius Ware, Antonio Dono, Roy Riascos-Castaneda, Nitin Tandon, Angel Blanco, Yoshua Esquenazi, Leomar Y. Ballester, Mark Amsbaugh, Arthur L. Day, and Jay-Jiguang Zhu
mutation is important for the proper selection of BRAF and MEK inhibitors. BRAF mutations have been grouped into 3 classes: class I comprises V600E mutations resulting in low RAS activity; class II includes BRAF fusions and non-V600E mutations, leading
Al B. Benson III, Alan P. Venook, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Ahmed Kamel, Lucille A. Leong, Edward Lin, Wells Messersmith, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Kristina M. Gregory, and Deborah A. Freedman-Cass
characterized by a specific mutation in the BRAF gene (V600E). 130 , 203 BRAF mutations are, for all practical purposes, limited to tumors that do not have KRAS exon 2 mutations. 203 , 204 Activation of the protein product of the nonmutated BRAF gene
Phillip G. Febbo, Marc Ladanyi, Kenneth D. Aldape, Angelo M. De Marzo, M. Elizabeth Hammond, Daniel F. Hayes, A. John Iafrate, R. Kate Kelley, Guido Marcucci, Shuji Ogino, William Pao, Dennis C. Sgroi, and Marian L. Birkeland
or predictive strength for the disease or class of therapy. One recent example of co-approval of a drug and companion diagnostic is the BRAF V600E mutation test coapproved with the kinase inhibitor vemurafenib. BRAF mutations are found in 30% to
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, Linda Farkas, Ignacio Garrido-Laguna, Jean L. Grem, Andrew Gunn, J. Randolph Hecht, Sarah Hoffe, Joleen Hubbard, Steven Hunt, Kimberly L. Johung, 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, Kristina M. Gregory, and Lisa A. Gurski
NCCN.org ). Currently, determination of tumor gene status for KRAS/NRAS and BRAF mutations, as well as HER2 amplifications and microsatellite instability high (MSI)/mismatch repair (MMR) status (if not previously done), are recommended for patients
Richard D. Carvajal, Sharon A. Spencer, and William Lydiatt
74% decrease in hazard of tumor progression. Importantly, vemurafenib is only effective in tumors driven by an activating BRAF mutation. Although BRAF mutations are present in 45% to 50% of CM, the prevalence is less than 10% in MM. 48 , 49 The
Johannes Uhlig, Michael Cecchini, Amar Sheth, Stacey Stein, Jill Lacy, and Hyun S. Kim
, 11 MSI and KRAS status therefore impact individualized treatment strategies for patients with CRC, particularly those with advanced or metastatic CRC (mCRC). Although BRAF mutations have also been described in mCRC, therapeutic targeting is
Zi-Xian Wang, Hao-Xiang Wu, Ming-Ming He, Ying-Nan Wang, Hui-Yan Luo, Pei-Rong Ding, Dan Xie, Gong Chen, Yu-Hong Li, Feng Wang, and Rui-Hua Xu
BRAF mutation with stratification for PTL was reported in the PRIME, 20050181, and TAILOR studies and was generally balanced between treatment arms across these studies. 17 , 19 The efficacy data of anti-EGFR therapy with stratification for both BRAF
