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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