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Cited by 132Colorectal Cancer Treatments and StudiesColorectal Cancer Surgical TreatmentsGenetic factors in colorectal cancer

Progression-Free Survival Remains Poor Over Sequential Lines of Systemic Therapy in Patients With BRAF-Mutated Colorectal Cancer

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Morris, Van, Overman, Michael J., Jiang, Zhi-Qin, Garrett, Christopher, Agarwal, Shweta, Eng, Cathy, Kee, Bryan, Fogelman, David +4 more·2014·Clinical Colorectal Cancer
DOI 10.1016/j.clcc.2014.06.001PMC PMC4266576
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Abstract

Background BRAF mutations occur in 5% to 10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described. Patients and methods We searched the M.D. Anderson Cancer Center databases for patients with colorectal cancer and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, PFS, overall survival, and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method. Results Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first 3 lines of chemotherapy, median PFS was 6.3 months (n = 69 patients; 95% confidence interval [CI], 4.9-7.7 months), 2.5 months (n = 58 patients; 95% CI, 1.8-3.0 months), and 2.6 months (n = 31 patients; 95% CI, 1.0-4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively; P = .99). Conclusion PFS is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present (with testing preferentially performed in patients suitable for clinical trials in refractory disease), these data provide historic controls suitable for future study design and support the idea that novel therapeutic options are essential in this population.

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  • BRAFV600E mutations are present in around 10% of advanced CRC patients and lead to constitutive activation of the MAPK pathway, drug resistance and a poor prognosis.

    “BRAFV600E mutations are present in around 10% of advanced CRC patients and lead to constitutive activation of the MAPK pathway, drug resistance and a poor prognosis [1–4].”

    From Co-targeting SRC overcomes resistance to BRAF inhibitors in colorectal cancer (2025) · cites this paper as [3]

    The Introduction (page not specified) reports BRAF mutations in 5%–10% of all colorectal tumors, identifies V600E as the most common mutation, and links BRAF mutations to constitutive MAPK activation and poor survival. It also reports low treatment response rates, but does not establish that V600E causes drug resistance; its prevalence estimate is for all colorectal tumors, not specifically advanced CRC. (LLM, conf=0.84)

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  • BRAFV600E mutations occur in approximately 10% of colorectal cancer patients and are associated with poor prognosis.

    “BRAFV600E mutations occur in ∼10% of colorectal cancer (CRC) patients, leading to poor prognosis.”

    From Co-targeting SRC overcomes resistance to BRAF inhibitors in colorectal cancer (2025) · cites this paper as [3]

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Cited by

Sorted by citations

Authors
Morris, V., Overman, M. J., Jiang, Z.-Q., Garrett, C., Agarwal, S., Eng, C., Kee, B., Fogelman, D., Dasari, A., Wolff, R., Maru, D., & Kopetz, S.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Kopetz, Scott
ORCID
Venue
Clinical Colorectal Cancer
Publisher
Elsevier BV
Published
2014-09
Volume
13
Issue
3
Pages
164-171
ISSN
1533-0028 (ISSN-L)
DOI
10.1016/j.clcc.2014.06.001
PMC
PMC4266576
OpenAlex
W1975946874
Cited by
132
References
5
Citations by year
2026: 3 · 2025: 8 · 2024: 8 · 2023: 12 · 2022: 16 · 2021: 19 · 2020: 17 · 2019: 18 · 2018: 4 · 2017: 9 · 2016: 10 · 2015: 7 · 2014: 1
FWCI
4.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Colorectal Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Health (CA16672)
  • Cancer Center Support
Topics
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
BRAF mutation, metastatic colorectal cancer, progression-free survival, oxaliplatin, irinotecan, prognostic factors, overall survival, ascertainment bias
MeSH terms
Cetuximab, Irinotecan, Oxaliplatin, Panitumumab, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Female, Humans, Liver Neoplasms, Lung Neoplasms, Lymphatic Metastasis, Male, Middle Aged, Mutation, Neoplasm Staging, Organoplatinum Compounds, Peritoneal Neoplasms, Biomarkers, Tumor, Colorectal Neoplasms, Survival Rate, Disease-Free Survival, Proto-Oncogene Proteins B-raf, Microsatellite Instability, Metastasectomy, Antibodies, Monoclonal, Humanized

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