BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/ Microsatellite High Colorectal Cancer

Elaine Tan, Junmin Whiting, Hao Xie, Iman Imanirad, Estrella Carballido, Seth Felder, Jessica Frakes, Quanxing Mo, Christine Walko, Jennifer B. Permuth, Katelyn Sommerer, Richard Kim, Daniel A. Anaya, Jason B. Fleming, Ibrahim Halil Sahin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC. Materials/Methods: This was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type. Results: There were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P < .001). Patients with age >50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P < .001). BRAF mutations and age >50 remained significant predictors of OS in multivariate analysis. Conclusion: BRAF mutations and age >50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes.

Original languageEnglish (US)
Pages (from-to)191-197
Number of pages7
JournalOncologist
Volume27
Issue number3
DOIs
StatePublished - Mar 2022
Externally publishedYes

Keywords

  • BRAF V600E
  • KRAS
  • NRAS
  • colorectal cancer
  • late-onset disease
  • microsatellite instability high
  • mismatch repair deficiency
  • prognosis

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/ Microsatellite High Colorectal Cancer'. Together they form a unique fingerprint.

Cite this