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Retrospective study of RAS/PIK3CA/BRAF tumor mutations as predictors of response to first-line chemotherapy with bevacizumab in metastatic colorectal cancer patients.

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  • معلومة اضافية
    • المصدر:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : BioMed Central, [2001-
    • الموضوع:
      Bevacizumab/*therapeutic use ; Class I Phosphatidylinositol 3-Kinases/*genetics ; Colorectal Neoplasms/*genetics ; Liver Neoplasms/*genetics ; Mutation/*genetics ; Proto-Oncogene Proteins B-raf/*genetics ; ras Proteins/*genetics; Adult ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Biomarkers, Tumor/genetics ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate
    • نبذة مختصرة :
      Background: After analysis of minor RAS mutations (KRAS exon 3, 4/NRAS) in the FIRE-3 and PRIME studies, an expanded range of RAS mutations were established as a negative predictive marker for the efficacy of anti-EGFR antibody treatment. BRAF and PIK3CA mutations may be candidate biomarkers for anti-EGFR targeted therapies. However, it remains unknown whether RAS/PIK3CA/BRAF tumor mutations can predict the efficacy of bevacizumab in metastatic colorectal cancer. We assessed whether selection according to RAS/PIK3CA/BRAF mutational status could be beneficial for patients treated with bevacizumab as first-line treatment for metastatic colorectal cancer.
      Methods: Of the 1001 consecutive colorectal cancer patients examined for RAS, PIK3CA, and BRAF tumor mutations using a multiplex kit (Luminex®), we studied 90 patients who received combination chemotherapy with bevacizumab as first-line treatment for metastatic colorectal cancer. The objective response rate (ORR) and progression-free survival (PFS) were evaluated according to mutational status.
      Results: The ORR was higher among patients with wild-type tumors (64.3%) compared to those with tumors that were only wild type with respect to KRAS exon 2 (54.8%), and the differences in ORR between patients with wild-type and mutant-type tumors were greater when considering only KRAS exon 2 mutations (6.8%) rather than RAS/PIK3CA/BRAF mutations (18.4%). There were no statistically significant differences in ORR or PFS between all wild-type tumors and tumors carrying any of the mutations. Multivariate analysis revealed that liver metastasis and RAS and BRAF mutations were independent negative factors for disease progression after first-line treatment with bevacizumab.
      Conclusions: Patient selection according to RAS/PIK3CA/BRAF mutations could help select patients who will achieve a better response to bevacizumab treatment. We found no clinical benefit of restricting combination therapy with bevacizumab for metastatic colorectal cancer patients with EGFR-wild type tumors.
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    • Contributed Indexing:
      Keywords: BRAF mutation; Colorectal cancer; PIK3CA mutation; RAS mutation; bevacizumab
    • الرقم المعرف:
      0 (Angiogenesis Inhibitors)
      0 (Biomarkers, Tumor)
      2S9ZZM9Q9V (Bevacizumab)
      EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
      EC 2.7.1.137 (PIK3CA protein, human)
      EC 2.7.11.1 (BRAF protein, human)
      EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
      EC 3.6.5.2 (ras Proteins)
    • الموضوع:
      Date Created: 20170111 Date Completed: 20171030 Latest Revision: 20220316
    • الموضوع:
      20231215
    • الرقم المعرف:
      PMC5223326
    • الرقم المعرف:
      10.1186/s12885-016-2994-6
    • الرقم المعرف:
      28068936