Abstract
BackgroundOutcomes 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.MethodsThis 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.ResultsOf 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.ConclusionsAntiangiogenic-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 registrationGIT-BRAF-2017-01.
Highlights
Outcomes are poorer in metastatic colorectal cancer patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear
First-line treatment showed no significant effect on overall survival (OS), antiangiogenic-based regimens were associated with prolonged median progression-free survival (PFS) versus non-antiangiogenic regimens
Eligibility criteria Patients were eligible for inclusion if they were over 18 years of age and had a confirmed diagnosis of metastatic colorectal cancer (mCRC) with the BRAF V600 mutation
Summary
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. The presence of BRAF mutations, which are present in 5–10% of patients with mCRC, is a known adverse prognostic factor, especially in the metastatic setting. Systemic inflammation is known to be prognostic of poor clinical outcomes in patients with CRC [4]. Abnormal acute inflammatory phase proteins (e.g. elevated C-reactive protein [CRP] and decreased serum albumin) and increased counts of neutrophils and platelets relative to lymphocytes have been associated with adverse outcomes [4]
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