The Real-Life Data of BRAF Mutation on the Treatment of Colorectal Cancer: a TOG Study

J Gastrointest Cancer. 2021 Sep;52(3):932-939. doi: 10.1007/s12029-020-00514-9.

Abstract

Purpose: Colorectal cancer is the third leading diagnosis accounting for nearly 10% of all new cancers worldwide. The distinct features among BRAF mutant colorectal cancers make these tumor groups hard to treat for oncologists. The median overall survival (OS) of these types of cancers is reported to be 9 to 14 months.

Methods: The study was declared on the Turkish Oncology Study Group Conference and approved. The patients' data was received from the centers who confirmed to participate. The BRAF-mutated patients were included in the study. The demographic features (age, gender, etc.), type of mutation, tumor localizations, histology, microsatellite instability (MSI) status, metastasis patterns chemotherapeutic agents and progression, and death times were recorded.

Results: Thirty-nine patients were enrolled in the study. Sixteen patients had concurrent KRAS mutations, while 7 had NRAS mutations. Most of the patients received doublet chemotherapies in combination with anti-VEGF agents in the first and second line of the treatment. There was a significant difference in OS according to the stage which showed a decreased survival in stage IV patients at the time of diagnosis. Concurrent KRAS mutation resulted in increased OS. The median OS was 47 and 24 months favoring the KRAS mutant group. The patients whose primary tumor operated had better survival when compared with other patients. The median OS of the operated group was 47 months, while the non-operated group was 24 months. Liver metastasis was related to worse prognosis at the time of diagnosis in univariate analysis.

Conclusion: In our study we found a high concurrent RAS mutation ratio in a BRAF mutant patient group which was different from prior studies. The concurrent mutations resulted in a favorable outcome in terms of OS which is also different from the current knowledge. More prospective studies are needed especially BRAF-mutated patient population and especially with concurrent RAS mutations.

Keywords: BRAF; Colon cancer; Concurrent mutation; KRAS; Real-life experience.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / therapeutic use
  • Genes, ras
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Mutation
  • Organoplatinum Compounds / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics*
  • Survival Rate
  • Turkey / epidemiology

Substances

  • Biomarkers, Tumor
  • Organoplatinum Compounds
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol