Effect of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF v600-mutated metastatic colorectal cancer: a real-world study in Spain

BMC Cancer. 2021 Jan 14;21(1):64. doi: 10.1186/s12885-020-07758-5.

Abstract

Background: Outcomes are poorer in metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear. This real-world study assessed the effects of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF V600-mutated mCRC.

Methods: This real-world, multicenter, retrospective, observational study included patients with BRAF V600-mutated mCRC treated in eight hospitals in Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS); overall response rate (ORR) and disease control rate (DCR) were also assessed. The effect of first- and second-line treatment type on OS, PFS, ORR, and DCR were evaluated, plus the impact of systemic inflammatory markers on these outcomes. A systemic inflammation score (SIS) of 1-3 was assigned based on one point each for platelet-lymphocyte ratio (PLR) ≥200, neutrophil-lymphocyte ratio (NLR) ≥3, and serum albumin < 3.6 g/dL.

Results: Of 72 patients, data from 64 were analyzed. After a median of 69.1 months, median OS was 11.9 months and median first-line PFS was 4.4 months. First-line treatment was triplet chemotherapy-antiangiogenic (12.5%), doublet chemotherapy-antiangiogenic (47.2%), doublet chemotherapy-anti-EGFR (11.1%), or doublet chemotherapy (18.1%). Although first-line treatment showed no significant effect on OS, antiangiogenic-based regimens were associated with prolonged median PFS versus non-antiangiogenic regimens. Negative predictors of survival with antiangiogenic-based treatment were NLR, serum albumin, and SIS 1-3, but not PLR. Patients with SIS 1-3 showed significantly prolonged PFS with antiangiogenic-based treatment versus non-antiangiogenic-based treatment, while those with SIS=0 showed no PFS benefit.

Conclusions: Antiangiogenic-based regimens, SIS, NLR, and albumin were predictors of survival in patients with mCRC, while SIS, NLR and serum albumin may predict response to antiangiogenic-based chemotherapy.

Trial registration: GIT-BRAF-2017-01.

Keywords: Antiangiogenic-based chemotherapy; BRAF V600E mutations; Metastatic colorectal cancer; Systemic inflammation score.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Blood Platelets / pathology
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / pathology*
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Neutrophils / pathology
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • Spain
  • Survival Rate

Substances

  • Angiogenesis Inhibitors
  • Biomarkers, Tumor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf