2017年11月
Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study
BRITISH JOURNAL OF CANCER
- 巻
- 117
- 号
- 10
- 開始ページ
- 1450
- 終了ページ
- 1458
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/bjc.2017.308
- 出版者・発行元
- NATURE PUBLISHING GROUP
Background: Patients with BRAF(V600E)-mutated metastatic colorectal cancer (mCRC) have a poorer prognosis as well as resistance to anti-EGFR antibodies. However, it is unclear whether BRAF mutations other than BRAF(V600E) (BRAF(non-V600E) mutations) contribute to anti-EGFR antibody resistance.
Methods: This study was composed of exploratory and inference cohorts. Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort.
Results: In the exploratory cohort, 31 candidate biomarkers, including KRAS/NRAS/BRAF mutations, were identified. Targeted resequencing of 150 patients in the inference cohort revealed 40 patients with RAS (26.7%), 9 patients with BRAF(V600E) (6.0%), and 7 patients with BRAF(non-V600E) mutations (4.7%), respectively. The response rates in RAS, BRAF(V600E), and BRAF(non-V600E) were lower than those in RAS/BRAF wild-type (2.5%, 0%, and 0% vs 31.9%). The median PFS in BRAF(non-V600E) mutations was 2.4 months, similar to that in RAS or BRAF(V600E) mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months).
Conclusions: Although BRAF(non-V600E) mutations identified were a rare and unestablished molecular subtype, certain BRAF(non-V600E) mutations might contribute to a lesser benefit of anti-EGFR monoclonal antibody treatment.
Methods: This study was composed of exploratory and inference cohorts. Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort.
Results: In the exploratory cohort, 31 candidate biomarkers, including KRAS/NRAS/BRAF mutations, were identified. Targeted resequencing of 150 patients in the inference cohort revealed 40 patients with RAS (26.7%), 9 patients with BRAF(V600E) (6.0%), and 7 patients with BRAF(non-V600E) mutations (4.7%), respectively. The response rates in RAS, BRAF(V600E), and BRAF(non-V600E) were lower than those in RAS/BRAF wild-type (2.5%, 0%, and 0% vs 31.9%). The median PFS in BRAF(non-V600E) mutations was 2.4 months, similar to that in RAS or BRAF(V600E) mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months).
Conclusions: Although BRAF(non-V600E) mutations identified were a rare and unestablished molecular subtype, certain BRAF(non-V600E) mutations might contribute to a lesser benefit of anti-EGFR monoclonal antibody treatment.
- リンク情報
- ID情報
-
- DOI : 10.1038/bjc.2017.308
- ISSN : 0007-0920
- eISSN : 1532-1827
- PubMed ID : 28972961
- Web of Science ID : WOS:000414550300007