BRAFV600E is the driver mutation for approximately 10% of colorectal cancers and is found more
often in right-sided disease and older patients.
1
,
2
,
3
The presence of this mutation is associated with a poor prognosis and resistance
to chemotherapy, especially in the metastatic setting.
4
,
5
,
6
Standard first line therapy in these patients has a significantly shorter overall
survival compared to patients with BRAF wild-type disease.
7
,8
Historically, subsequent lines of chemotherapy have shown limited efficacy with median
progression free survival (PFS) of 2 to 3 months and overall survival (OS) of around
4 to 6 months.
9
,10
The addition of an EGFR tyrosine kinase inhibitor to the therapeutic regimen did not have any benefit in
PFS or OS.
11
,12
- Peeters M
- Oliner KS
- Price TJ
- et al.
Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared
with FOLFIRI alone as second-line treatment for metastatic colorectal cancer.
Clin Cancer Res Off J Am Assoc Cancer Res. 2015; 21: 5469-5479https://doi.org/10.1158/1078-0432.CCR-15-0526
Keywords
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References
- Clinical sequencing defines the genomic landscape of metastatic colorectal cancer.Cancer Cell. 2018; 33 (e3): 125-136https://doi.org/10.1016/j.ccell.2017.12.004
- Mutations of the BRAF gene in human cancer.Nature. 2002; 417: 949-954https://doi.org/10.1038/nature00766
- Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation.Int J Cancer. 2011; 128: 2075-2084https://doi.org/10.1002/ijc.25555
- 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: 753-762https://doi.org/10.1016/S1470-2045(10)70130-3
- 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: 715-721https://doi.org/10.1038/sj.bjc.6605177
- BRAF mutant colorectal cancer as a distinct subset of colorectal cancer: clinical characteristics, clinical behavior, and response to targeted therapies.J Gastrointest Oncol. 2015; 6: 660-667https://doi.org/10.3978/j.issn.2078-6891.2015.077
- Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer.N Engl J Med. 2014; 371: 1609-1618https://doi.org/10.1056/NEJMoa1403108
- FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study.Lancet Oncol. 2015; 16: 1306-1315https://doi.org/10.1016/S1470-2045(15)00122-9
- Progression-free survival remains poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer.Clin Colorectal Cancer. 2014; 13: 164-171https://doi.org/10.1016/j.clcc.2014.06.001
- Analysis of efficacy and prognostic factors in second-line chemotherapy for BRAF V600E mutant metastatic colorectal cancer.Ann Oncol. 2017; 28: v180https://doi.org/10.1093/annonc/mdx393.058
- Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial.Lancet Oncol. 2013; 14: 749-759https://doi.org/10.1016/S1470-2045(13)70163-3
- Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer.Clin Cancer Res Off J Am Assoc Cancer Res. 2015; 21: 5469-5479https://doi.org/10.1158/1078-0432.CCR-15-0526
- Management of BRAF-mutant metastatic colorectal cancer: a review of treatment options and evidence-based guidelines.Ann Oncol. 2021; 32: 959-967https://doi.org/10.1016/j.annonc.2021.03.206
- Encorafenib, and Cetuximab triplet therapy for patients with BRAF V600E–mutant metastatic colorectal cancer: safety lead-in results from the phase III BEACON colorectal cancer study.J Clin Oncol. 2019; 37: 1460-1469https://doi.org/10.1200/JCO.18.02459
- Binimetinib, and Cetuximab in BRAF V600E-Mutated colorectal cancer.N Engl J Med. 2019; 381: 1632-1643https://doi.org/10.1056/NEJMoa1908075
- Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-Mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study.J Clin Oncol Off J Am Soc Clin Oncol. 2021; 39: 273-284https://doi.org/10.1200/JCO.20.02088
- Randomized trial of irinotecan and cetuximab with or without Vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406).J Clin Oncol Off J Am Soc Clin Oncol. 2021; 39: 285-294https://doi.org/10.1200/JCO.20.01994
- Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: a phase 2 single-arm clinical trial.JAMA Oncol. 2019; 5: 343-350https://doi.org/10.1001/jamaoncol.2018.5080
- Phase II study of anti-EGFR rechallenge therapy with panitumumab driven by circulating tumor DNA molecular selection in metastatic colorectal cancer: The CHRONOS trial.J Clin Oncol. 2021; 39: 3501-3506https://doi.org/10.1200/JCO.2021.39.15_suppl.3506
- ctDNA applications and integration in colorectal cancer: an NCI colon and rectal–anal task forces whitepaper.Nat Rev Clin Oncol. 2020; 17: 757-770https://doi.org/10.1038/s41571-020-0392-0
- Circulating Tumor DNA analysis in colorectal cancer: from dream to reality.JCO Precis Oncol. 2019; : 1-14https://doi.org/10.1200/PO.18.00397
- Acquired RAS or EGFR mutations and duration of response to EGFR blockade in colorectal cancer.Nat Commun. 2016; 7: 13665https://doi.org/10.1038/ncomms13665
- Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients.Nat Med. 2015; 21: 795-801https://doi.org/10.1038/nm.3870
- Combined BRAF, EGFR, and MEK inhibition in patients with BRAFV600E-mutant colorectal cancer.Cancer Discov. 2018; 8: 428-443https://doi.org/10.1158/2159-8290.CD-17-1226
- Utility of circulating tumor DNA in the clinical management of patients with BRAF V600E metastatic colorectal cancer.J Clin Oncol. 2021; 39: 110-119https://doi.org/10.1200/JCO.2021.39.3_suppl.119
- BRAF mutation status in circulating tumor DNA from patients with metastatic colorectal cancer: extended mutation analysis from the AGEO RASANC study.Cancers. 2019; 11: E998https://doi.org/10.3390/cancers11070998
Article info
Publication history
Published online: December 31, 2021
Accepted:
December 11,
2021
Received in revised form:
December 7,
2021
Received:
October 13,
2021
Footnotes
Submitted: Oct 13, 2012; Revised: Dec 7, 2021; Accepted: Dec 11, 2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.