Th17 cell pathway-related genetic variants in metastatic colorectal cancer: A meta-analysis using TRIBE, MAVERICC, and FIRE-3.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 594-594
Author(s):  
Ryuma Tokunaga ◽  
Shu Cao ◽  
Francesca Battaglin ◽  
Jae Ho Lo ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Meta Analysis ◽  
Candidate Snps ◽  
First Line ◽  
Q Statistic ◽  
Line Chemotherapy

594 Background: Th17 cells constitute a subset of T-helper cells, and play a role in immune response to extracellular pathogens in the human intestinal tract. Further, Th17 cells are associated with tumor angiogenesis and enhanced efficacy of 5-FU treatment. We thus investigated associations between the Th17 cell pathway-related SNPs and clinical outcomes in patients with metastatic colorectal cancer (mCRC) treated with conventional chemotherapy. Methods: We analyzed a total of 884 patients with mCRC enrolled in three randomized clinical trials (TRIBE, MAVERICC, and FIRE-3: where patients were treated with FOLFIRI, mFOLFOX6, or FOLFOXIRI combined with bevacizumab or cetuximab as the first-line chemotherapy). Multivariable logistic regression and Cox regression were performed to evaluate the association between candidate SNPs in the Th17 cell pathway and clinical outcomes [tumor response (TR), progression-free survival (PFS), and overall survival (OS)] in each treatment cohort. The meta-analysis approach using the METASOFT software were implemented to quantify the prognostic effect of each SNP using the inverse-variance-weighted effect size, and also to evaluate the heterogeneity across cohorts using the Q statistic. SNPs were coded as additive, dominant, or recessive in the analysis. The Pegasus analysis was also used to identify effects across multiple SNPs and treatment arms. Results: Pathway analysis showed that the Th17 cell pathway was significantly associated with TR ( P = 0.011). There were suggestive associations of IL17F rs763780 with TR (log OR = 0.64, SE = 0.31; P = 0.038), of IL23R rs10889677 with TR (log OR = 0.37, SE = 0.18; P = 0.039), of IRF4 rs872071 with TR (log OR = -0.26, SE = 0.13; P = 0.037), and of IL21 rs2221903 with PFS (log HR = 0.33, SE = 0.15; P = 0.026), although these results were not significant after FDR adjustment. In addition, IL23R rs10889677 had suggestive heterogeneity of effects for PFS across the six cohorts after Cochran’s Q statistic ( P = 0.013). Conclusions: Th17 cell pathway-related SNPs may be predictors for the first-line chemotherapy in mCRC. Upon validation, our findings would provide novel insight for selecting treatment strategies for mCRC.

Early rise in blood pressure to predict clinical outcomes in metastatic colorectal cancer (mCRC) patients treated with first-line bevacizumab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14166-e14166
Author(s):  
Nazeerahamad N. Upanal ◽  
Stephen P. Ackland ◽  
Antonino Bonaventura ◽  
Patrick McElduff
Keyword(s):  
Colorectal Cancer ◽  
Blood Pressure ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Significant Rise ◽  
First Line ◽  
Early Rise ◽  
Line Chemotherapy

e14166 Background: Bevacizumab (Bev) induced hypertension (HTN) may be a predictive biomarker of anti-tumor activity in patients with metastatic colorectal cancer (mCRC) . We retrospectively assessed if significant rise in blood pressure (SRBP) [ ≥ 20 mmHg ] or any grade of HTN within first 10 weeks of treatment with bev is associated with improved clinical outcomes. Methods: Retrospective review of all mCRC patients, on or off clinical trial, treated with first line chemotherapy plus Bev (5 mg/kg Q2W or 7.5 mg/kg Q3W) at our institution from 2005-2010 was conducted .BP was measured before each treatment and graded according to CTCAE version 3.0.The median follow-up time of eligible patients was 19.6 months. Results: Of 50 patients eligible for the analysis, 20 patients (40%) developed significant rise in BP or HTN (SRH) whereas 30 patients had no change (NRH). There were no statistical differences between the two groups with respect to age, gender, ECOG status, number of sites of metastases, pre-existing HTN (55% SRH,37% NRH ; P=0.251) and first line chemotherapy regimen. Chemotherapy regimens used in SRH and NRH groups were 5-Fluoropyrimidine based (25% vs 23.3%), irinotecan based (40% vs. 36.7%) and oxaliplatin based (35% vs 30%). Four patients (20%) in the SRH group developed SRBP and other patients in this group developed G1-G3 HTN according to CTCAE v3.0.SRH group had improved median progression free survival (15.8 vs 6.2 months ; p<0.001) and overall survival (25.9 vs. 16 months; p=0.005). Overall response rate was higher in the SRH group (75% vs 26.7%; p=0.001). Conclusions: SRH developing within 10 weeks of commencing first line chemotherapy with bev correlates with improved outcomes in mCRC. These data need confirmation in prospective studies.

scholarly journals Bevacizumab-based first-line chemotherapy in elderly patients with metastatic colorectal cancer: an individual patient data based meta-analysis

Oncotarget ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 10272-10283 ◽  
Author(s):  
Christine Koch ◽  
Anna M. Schwing ◽  
Eva Herrmann ◽  
Markus Borner ◽  
Eduardo Diaz-Rubio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
First Line ◽  
Line Chemotherapy

scholarly journals Efficacy of Adding Bevacizumab in the First-Line Chemotherapy of Metastatic Colorectal Cancer: Evidence from Seven Randomized Clinical Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yan-xian Chen ◽  
Qiong Yang ◽  
Jun-jie Kuang ◽  
Shi-yu Chen ◽  
Ying Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Subgroup Analysis ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Current Data ◽  
Cochrane Library ◽  
First Line ◽  
First Line Therapy ◽  
Line Chemotherapy

Background. Efficacy of adding bevacizumab in first-line chemotherapy of metastatic colorectal cancer (mCRC) has been controversial. The aim of this study is to gather current data to analyze efficacy of adding bevacizumab to the most used combination first-line chemotherapy in mCRC, based on the 2012 meta-analysis reported by Macedo et al.  Methods. Medline, EMBASE and Cochrane library, meeting presentations and abstracts were searched. Eligible studies were randomized controlled trials (RCTs) which evaluated first-line chemotherapy with or without bevacizumab in mCRC. The extracting data were included and examined in the meta-analysis according to the type of chemotherapy regimen.Results. Seven trials, totaling 3436 patients, were analyzed. Compared with first-line chemothery alone, the adding of bevacizumab did not show clinical benefit for OS both in first-line therapy and the most used combination chemotherapy (HR = 0.89; 95% CI = 0.78–1.02;P=0.08; HR = 0.93; 95% CI = 0.83–1.05;P=0.24). In contrast with OS, the addition of bevacizumab resulted in significant improvement for PFS (HR = 0.68; 95% CI = 0.59–0.78;P<0.00001). Moreover, it also demonstrated statistical benefit for PFS in the most used combination first-line chemotherapy (HR = 0.84; 95% CI = 0.75–0.94;P=0.002). And the subgroup analysis indicated only capacitabine-based regimens were beneficial.Conclusions. This meta-analysis shows that the addition of bevacizumab to FOLFOX/FOLFIRI/XELOX regimens might not be beneficial in terms of OS. Benefit has been seen when PFS has been taken into account. In subgroup analysis, benefit adding bevacizumab has been seen when capecitabine-based regimens are used. Further studies are warranted to explore the combination with bevacizumab.

The nationwide screening project on plasma angiogenesis-related mediators for treatment selection of optimal antiangiogenic inhibitors in metastatic colorectal cancer: GI-SCREEN CRC-Ukit.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS885-TPS885
Author(s):  
Satoshi Yuki ◽  
Kentaro Yamazaki ◽  
Hiroya Taniguchi ◽  
Yu Sunakawa ◽  
Akihito Kawazoe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Adhesion Molecule ◽  
Second Line ◽  
First Line ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal ◽  
Line Chemotherapy

TPS885 Background: Antiangiogenic treatments are a proven useful tool to improve clinical outcomes in patients (pts) with metastatic colorectal cancer (mCRC). Recently, higher levels of vascular endothelial growth factor-D (VEGF-D) are a potential predictive biomarker for ramucirumab efficacy on overall and progression-free survival in mCRC (Tabernero J, et al. ESMO 2017). However, there are limited data on mCRC associating the efficacy of antiangiogenic therapy with angiogenesis-related mediators, such as VEGF family members and their receptors, and with dynamic transition among these mediators during clinical courses. In addition, immune-related factors such as interferon gamma (IFNγ) and transforming growth factor β1 (TGFβ1) may be associated with the regulation of angiogenesis. Methods: This prospective longitudinal study aims to investigate the association between plasma angiogenesis-related mediators and clinical outcomes in mCRC. The key eligibility criteria include pts with mCRC who will receive one of the following regimens: first-line chemotherapy plus bevacizumab, first-line chemotherapy plus anti-EGFR antibody (either cetuximab or panitumumab), second-line FOLFIRI plus ramucirumab, second-line FOLFIRI plus aflibercept, or second-line chemotherapy plus bevacizumab. Plasma is collected twice in pairs from all pts pre- and post-treatment. Comprehensive measurements of plasma angiogenesis-related mediators, such as placental growth factor (PlGF), hepatocyte growth factor (HGF), IL-6, IL-8, angiopoietin-2, neuropillin-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), thrombospondin-2 (TSP-2), osteopontin (OPN), sVEGFR-1, sVEGFR-2, sVEGFR-3, VEGF-A, VEGF-D, as well as key targets associated with immunotherapy such as IFNγ and TGFβ1 are analyzed in parallel by the multiplex assay with Luminex® technology. The target sample size is 1,000. This study was initiated in September 2017. Clinical trial information: UMIN000028616.

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