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

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.

Real-World Study: A Powerful Tool for Malignant Tumor Research in General Surgery

“…In terms of prognosis, a multicenter RWS found that antiangiogenic-based regimens prolonged median PFS in patients with mCRC, while the systemic inflammation score, neutrophil–lymphocyte ratio (NLR) and serum albumin could predict the efficacy of treatment [ 79 ]. In addition, the study also confirmed that patients with BRAF mutations responded poorly to treatment than wild-type (WT) BRAF tumors, resulting in a worse prognosis [ 79 ]. A retrospective study also confirmed that in mCRC patients, WT patients have higher OS [ 80 ].…”

The Systemic Inflammation Score is Associated with the Survival of Patients with Prostate Cancer

“…[20][21][22] The preoperative SIS was shown to be an effective prognostic factor in many cancers. 19,[23][24][25][26] However, studies on the ability of the SIS system to predict the survival of PCa patients have not been reported. Thus, in this study, we elucidated the prognostic effect of the pretherapeutic SIS in patients with PCa in a Chinese Han population.…”

“…24 Galizia et al suggested that the SIS system was not associated with the survival of CRC patients in a multivariate analysis. 27 In addition, two studies 25,26 utilized a modified SIS system with 19 However, those studies obtained conflicting results regarding OS. 25,26 Martínez-Lago et al showed that the SIS was a prognostic factor for OS, 26 while Wang et al found that the SIS was not associated with the survival of CRC.…”

“…27 In addition, two studies 25,26 utilized a modified SIS system with 19 However, those studies obtained conflicting results regarding OS. 25,26 Martínez-Lago et al showed that the SIS was a prognostic factor for OS, 26 while Wang et al found that the SIS was not associated with the survival of CRC. 25 Several studies have used the SIS or modified SIS system to evaluate the prognosis of gastric cancer (GC).…”

“…In this study, we found that a high SIS was a prognostic factor for adverse OS in patients with PCa, which was partly in line with findings for other cancers. 19,26,28,35 We assumed that a higher SIS reflected persistent inflammation and impaired nutrition, which negatively affected PCa prognosis.…”