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.
Adult
Aged
Aged, 80 and over
Angiogenesis Inhibitors
/ therapeutic use
Biomarkers, Tumor
/ analysis
Blood Platelets
/ pathology
Colorectal Neoplasms
/ drug therapy
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
Antiangiogenic-based chemotherapy
BRAF V600E mutations
Metastatic colorectal cancer
Systemic inflammation score
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
14 Jan 2021
14 Jan 2021
Historique:
received:
18
09
2020
accepted:
21
12
2020
entrez:
15
1
2021
pubmed:
16
1
2021
medline:
11
5
2021
Statut:
epublish
Résumé
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. 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. 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. 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. GIT-BRAF-2017-01.
Sections du résumé
BACKGROUND
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
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
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
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
BACKGROUND
GIT-BRAF-2017-01.
Identifiants
pubmed: 33446148
doi: 10.1186/s12885-020-07758-5
pii: 10.1186/s12885-020-07758-5
pmc: PMC7807898
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Biomarkers, Tumor
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Multicenter Study
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
64Subventions
Organisme : GITuD
ID : medical writing assistance
Références
J BUON. 2019 Sep-Oct;24(5):1861-1869
pubmed: 31786848
World J Gastroenterol. 2019 Aug 21;25(31):4383-4404
pubmed: 31496619
Eur J Cancer. 2015 Mar;51(5):587-94
pubmed: 25673558
N Engl J Med. 2019 Oct 24;381(17):1632-1643
pubmed: 31566309
Ann Oncol. 2010 Dec;21(12):2396-2402
pubmed: 20501503
N Engl J Med. 2015 Aug 20;373(8):726-36
pubmed: 26287849
J Clin Oncol. 2011 May 20;29(15):2011-9
pubmed: 21502544
World J Gastrointest Surg. 2015 Dec 27;7(12):370-7
pubmed: 26730282
Eur J Cancer. 2012 Jul;48(10):1466-75
pubmed: 22446022
J Clin Oncol. 2020 Dec 23;:JCO2001994
pubmed: 33356422
Br J Cancer. 2015 Jun 9;112(12):1966-75
pubmed: 25973534
Br J Cancer. 2015 Jun 9;112(12):1888-94
pubmed: 25989278
Oncology (Williston Park). 2019 Jun 19;33(6):206-11
pubmed: 31219603
Nat Med. 2015 Nov;21(11):1350-6
pubmed: 26457759
J Clin Oncol. 2015 Dec 1;33(34):4032-8
pubmed: 26460303
Ann Oncol. 2015 Jun;26(6):1201-1207
pubmed: 25735317
Int J Colorectal Dis. 2007 Aug;22(8):881-6
pubmed: 17245566
Clin Cancer Res. 2015 Mar 15;21(6):1313-20
pubmed: 25589621
Sci Rep. 2019 Dec 30;9(1):20326
pubmed: 31889159
Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1792-8
pubmed: 22899730
World J Gastroenterol. 2015 Nov 21;21(43):12410-20
pubmed: 26604648
Cancers (Basel). 2020 Apr 21;12(4):
pubmed: 32326305
Clin Colorectal Cancer. 2018 Mar;17(1):50-57.e8
pubmed: 29096990
Ann Oncol. 2016 Aug;27(8):1386-422
pubmed: 27380959
Cancer Discov. 2012 Mar;2(3):227-35
pubmed: 22448344