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Response to Anti-EGFR Therapy in Patients with BRAF non-V600–Mutant Metastatic Colorectal Cancer
- Source :
- Clin Cancer Res
- Publication Year :
- 2019
- Publisher :
- American Association for Cancer Research (AACR), 2019.
-
Abstract
- Purpose: While mutations in BRAF in metastatic colorectal cancer (mCRC) most commonly occur at the V600 amino acid, with the advent of next-generation sequencing, non-V600 BRAF mutations are increasingly identified in clinical practice. It is unclear whether these mutants, like BRAF V600E, confer resistance to anti-EGFR therapy. Experimental Design: We conducted a multicenter pooled analysis of consecutive patients with non-V600 BRAF-mutated mCRCs identified between 2010 and 2017. Non-V600 BRAF mutations were divided into functional classes based on signaling mechanism and kinase activity: activating and RAS-independent (class 2) or kinase-impaired and RAS-dependent (class 3). Results: Forty patients with oncogenic non-V600 BRAF–mutant mCRC received anti-EGFR antibody treatment [n = 12 (30%) class 2 and n = 28 (70%) class 3]. No significant differences in clinical characteristics were observed by mutation class. In contrast, while only 1 of 12 patients with class 2 BRAF mCRC responded, 14 of 28 patients with class 3 BRAF responded to anti-EGFR therapy (response rate, 8% and 50%, respectively, P = 0.02). Specifically, in first- or second-line, 1 of 6 (17%) patients with class 2 and 7 of 9 (78%) patients with class 3 BRAF mutants responded (P = 0.04). In third- or later-line, none of 6 patients with class 2 and 7 of 19 (37%) patients with class 3 BRAF mutants responded (P = 0.14). Conclusions: Response to EGFR antibody treatment in mCRCs with class 2 BRAF mutants is rare, while a large portion of CRCs with class 3 BRAF mutants respond. Patients with colorectal cancer with class 3 BRAF mutations should be considered for anti-EGFR antibody treatment. See related commentary by Fontana and Valeri, p. 6896
- Subjects :
- Male
Proto-Oncogene Proteins B-raf
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
endocrine system diseases
Colorectal cancer
Mutant
Cetuximab
Mice, SCID
medicine.disease_cause
Article
EGFR Antibody
03 medical and health sciences
0302 clinical medicine
Mice, Inbred NOD
Internal medicine
Tumor Cells, Cultured
medicine
Animals
Humans
Molecular Targeted Therapy
Prospective Studies
Kinase activity
Prospective cohort study
Protein Kinase Inhibitors
neoplasms
Survival rate
Mutation
biology
Rectal Neoplasms
business.industry
Prognosis
medicine.disease
Xenograft Model Antitumor Assays
digestive system diseases
ErbB Receptors
Survival Rate
030104 developmental biology
030220 oncology & carcinogenesis
Colonic Neoplasms
biology.protein
Female
Antibody
Colorectal Neoplasms
business
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....83bd74f6eb04f8555c45047727ea594e