Response to anti-EGFR therapy in patients with BRAF non-V600–mutant metastatic colorectal cancer Journal Article


Authors: Yaeger, R.; Kotani, D.; Mondaca, S.; Parikh, A. R.; Bando, H.; Van Seventer, E. E.; Taniguchi, H.; Zhao, H.; Thant, C. N.; de Stanchina, E.; Rosen, N.; Corcoran, R. B.; Yoshino, T.; Yao, Z.; Ebi, H.
Article Title: Response to anti-EGFR therapy in patients with BRAF non-V600–mutant metastatic colorectal cancer
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 1⁄4 12 (30%) class 2 and n 1⁄4 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 1⁄4 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 1⁄4 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 1⁄4 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. © 2019 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 25
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2019-12-01
Start Page: 7089
End Page: 7097
Language: English
DOI: 10.1158/1078-0432.Ccr-19-2004
PUBMED: 31515458
PROVIDER: scopus
PMCID: PMC6891165
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Neal Rosen
    398 Rosen
  2. Rona Denit Yaeger
    164 Yaeger
  3. Zhan Yao
    37 Yao
  4. HuiYong   Zhao
    15 Zhao
  5. Claire Thant
    2 Thant