BRAF mutations can deepen the danger in mCRC

BRAF mutations can deepen the danger in mCRC
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Patients with mCRC harboring BRAF V600 mutations exhibit overall survival rates half that of patients with wild-type BRAF1

Outcomes in patients with BRAF-mutant mCRC are generally poor in later lines of therapy using products currently approved for mCRC patients2-4
overall survival (OS) is 4 to 6 months
progression-free survival (PFS) is 2-3 months
overall response rate (ORR) is 4% to 8%

mCRC, metastatic colorectal cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free.

Discover the danger of BRAF mutations

Because of the strong prognostic value in determining the presence of a BRAF mutation, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend that all patients with mCRC should be tested at diagnosis5,6

mCRC, metastatic colorectal cancer; NCCN, National Comprehensive Cancer Network.

Knowing can make a difference

Research is ongoing to identify strategies that optimally suppress MAPK signaling7,8

Deepen your understanding
References:
1. Safaee Ardekani G, Jafarnejad SM, Tan L, Saeedi A, Li G. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS ONE. 2012;7(10):e47054. 2. Loupakis F, Ruzzo A, Cremolini C, et al. KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer. 2009;101(4):715-721. 3. De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11(8):753-762. 4. Clinicaltrials.gov. US National Library of Medicine. S1406 phase II study of irinotecan and cetuximab with or without vemurafenib in BRAF mutant metastatic colorectal cancer. https://clinicaltrials.gov/ct2/show/results/NCT02164916. Accessed December 14, 2018. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.4.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed December 19, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed December 19, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 7. Ursem C, Atreya CE, Van Loon K. Emerging treatment options for BRAF-mutant colorectal cancer. Gastrointest Cancer. 2018;8:13-23. 8. Corcoran RB, André T, Atreya CE, et al. Combined BRAF, EGFR, and MEK inhibition in patients with BRAFV600E-mutant colorectal cancer. Cancer Discov. 2018;8(4):428-443. 9. Corcoran RB, Ebi H, Turke AB, et al. EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov. 2012;2(3):227-235. 10. National Cancer Institute. SEER cancer stat facts: colorectal cancer. https://seer.cancer.gov/statfacts/html/colorect.html. Accessed November 1, 2018. 11. Zadlo, J. Cost-effectiveness of new and emerging treatment options for the treatment of metastatic colorectal cancer. Am J Manag Care. 2018;24(suppl 7):S118-S124. 12. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386-1422. 13. Dinu D, Dobre M, Panaitescu E, et al. Prognostic significance of KRAS gene mutations in colorectal cancer—preliminary study. J Med Life. 2014;7(4):581-587. 14. Tran B, Kopetz S, Tie J, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011;117(20):4623-4632. 15. Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483(7387):100-103.