What is the role of the anti-angiogenic therapy in BRAF (V600E) mutant metastatic colorectal cancer patients in a real-world setting?

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 620-620 ◽  
Author(s):  
Nieves Martinez Lago ◽  
Marta Covela Rúa ◽  
Elena Brozos Vazquez ◽  
Ana Fernandez Fernandez Montes ◽  
Juan Cruz De La Camara Gomez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Strong Predictor ◽  
Tumor Resection ◽  
Braf V600e ◽  
Prognostic Impact ◽  
First Line ◽  
Multicentric Study ◽  
Real World Setting

620 Background: Activating B-type Raf kinase (BRAF) mutations, mostly missense V600E, occur in approximately 8% to 12% of patients with metastatic colorectal cancer (mCRC). BRAF (V600E)mt is a strong predictor of a poor prognosis, with distinct clinical and pathological features. However, it is unknown whether this mutation is predictive of any treatment benefit in a real world setting. Methods: We conducted an observational, retrospective, multicentric study of patients with BRAF V600E-mt mCRC treated at nine university Spanish hospitals in NW Spain, belonging to GITuD (Galician Research Group on Digestive Tumors). Demographic, clinic and pathological characteristics, overall survival (OS) and first-line progression free survival (PFS) were retrospectively collected and analyzed. Results: Data from 65 patients treated between November 2010 to June 2018 were recorded in this study. Median age was 62.8 years (range 30-83 years), 55.4 % female, 75.4% ECOG PS0-1, 49.2% right-sided, 35.2% high grade, 69.2% synchronous presentation, 66.2% primary tumor resection and median metastatic locations was 2 (range 1-5). With a median follow up of 64.6 months, median OS was 12.9 months (95% CI, 9.8-16.0 months) and first line PFS was 4.1 months (95% CI, 2.7-5.5 months). First line PFS according treatment: Bev+Triplet-CT/Bev+Doublet-CT/antiEGFR+Doublet-CT/Doublet-CT: 6.2 vs 4.8 vs 2.9 vs 2.1 months (p = 0.020). Bevacizumab based chemotherapy was associated with a prolonged first line PFS (median 5.0 vs. 2.1 months, HR, 0.406; 95% CI, 0.20-0.81; p = 0.005). Nevertheless, no statistical differences between bevacizumab based regimes, (Triplet-CT vs Doublet-CT (HR 0.830; 95% CI 0.4-1.9; p = 0.666)) or between Doublet-CT with or without a antiEGFR were found (HR 0.511; 95% CI 0.2-1.6; p = 0.223). Conclusions: Our study confirms the negative prognostic impact of BRAF V600Emt in mCRC and encourage the use of anti-angiogenic based chemotherapy in this subgroup of patients.

The prognostic value of systemic inflammatory factors in BRAF (V600E) mutant metastatic colorectal cancer (mCRC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 622-622
Author(s):  
Nieves Martinez Lago ◽  
Marta Covela Rúa ◽  
Elena Brozos Vazquez ◽  
Ana Fernandez Fernandez Montes ◽  
Juan Cruz de la Cámara Gómez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Metastatic Colorectal Cancer ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Inflammatory Factors ◽  
Prognostic Impact ◽  
Multicentric Study ◽  
Lymphocyte Ratio

622 Background: Multiple studies have reported prognostic association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLT) and albumin levels including patients with early and advanced metastatic colorectal cancer. However, it is unknown the prognostic impact in patients with BRAF (V600E) mutant metastatic colorectal cancer (mCRC). Methods: We conducted an observational, retrospective, multicentric study of patients with BRAF V600E-mt mCRC treated at nine university Spanish hospitals belonging to GITuD (Galician Research Group on Digestive Tumors). Demographic, clinic, pathological characteristics, overall survival (OS) and progression free survival (PFS) data were retrospectively analyzed. Results: Data from 65 pts. treated between November 2010 to June 2018 were recorded. Median age was 62.8 years (range 30-83), 55.4 % female, 75.4% ECOG PS0-1, 49.2% right-sided, 35.2% high grade, 69.2% synchronous presentation, 66.2% primary tumor resection and median metastatic locations was 2 (range 1-5). With a median follow up of 64.6 months, median OS was 12.9 months (95% CI, 9.8-16.0) and first line PFS was 4.1 months (95% CI, 2.7-5.5). NLR (HR 2.294; p = 0.004), PLR (HR 6.329; p = 0.028) and albumin levels (HR 2.575, p = 0.011) were independent prognostic factors for OS. Patients with higher NLR (> 3 vs. < 3): had a significantly lower OS 6.8 versus 17.5 months (HR 2.294; 95% CI 1.3-4.1, p = 0.004), which was also true for patients with higher PLR (> 200 vs. < 200): with OS 6.3 versus 14.5 months (HR 1.879; 95% CI 1.1-3.3, p = 0.028), while patients with low albumin had lower OS 6.8 versus 13.4 months (HR 2.575; 95% CI 1.2-5.5, p = 0.011). NLR was positively associated with PLR (p < 0.001). Neither NLR (p = 0.190) or PLR (p = 0.327) were associated with low albumin levels. A Systemic Inflammation Score (assigning one point for each factor) was predictive of survival: OS 0/1/2/3 factors were 17.7 versus 8.7 versus 9.7 versus 5.0 months (p < 0.001). Patients with Systemic Inflamation Score = 0 had significantly higher OS: 17.7 versus 8.2 months (HR 0.357; 95% CI 0.2-0.7, p = 0.001). Conclusions: NLR, PLR and albumin levels are significant prognostic factors in patients with BRAF V600E-mt mCRC.

Survival impact on regorafenib (REG) and trifluridine/tipiracil hydrochloride (FTD/TPI) for patients with metastatic colorectal cancer: Single institutional experience.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 43-43
Author(s):  
Keigo Chida ◽  
Daisuke Kotani ◽  
Kentaro Sawada ◽  
Yoshiaki Nakamura ◽  
Akihito Kawazoe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Phase Iii ◽  
First Line ◽  
Standard Chemotherapy ◽  
Exon 2 ◽  
The Real ◽  
Real World Setting ◽  
Tipiracil Hydrochloride

43 Background: Regorafenib (REG) and trifluridine/tipiracil hydrochloride (FTD/TPI) demonstrated overall survival (OS) benefit in patients (pts) with metastatic colorectal cancer (mCRC) in the CORRECT and RECOURSE phase III trials. In Japan, REG and FTD/TPI have been approved in 2013 and 2014, respectively. However, little is known about survival impact on these agents in the real-world setting. Therefore, the aim of this retrospective study was to evaluate the effects of REG and FTD/TPI in pts with mCRC. Methods: We collected medical records from consecutive 1142 pts who had been initiated with first-line chemotherapy for mCRC from 2008 to 2016 at National Cancer Center Hospital East. The survival outcomes were compared between pts from 2008 to 2011 (cohort A) and those from 2012 to 2016 (cohort B). This study excluded pts who have not been refractory or intolerant to standard chemotherapy including fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR antibody if KRAS exon 2/ RAS wild-type tumors. Results: A total of 590 pts were analyzed (cohort A; N = 236 and cohort B; N = 354). More patients received at least one of REG or FTD/TPI in cohort B (16.1% vs. 59.9%, p < 0.001). The time from initiation to end of standard chemotherapy was comparable between the two cohort (20.0 vs. 17.5 months, p = 0.266). With a median follow-up period of 34.9 months, salvage-line OS (sOS) after standard chemotherapy was significantly longer in cohort B (4.8 vs. 6.6 months, p = 0.001), while there was only a favorable trend in cohort B in terms of OS from start of first-line treatment (27.3 vs. 28.5 months, p = 0.516). In cohort B, pts who sequentially received both of REG and FTD/TPI showed longest sOS (median, both of REG and FTD/TPI; 11.3 months, either REG or FTD/TPI; 7.0 months, neither REG nor FTD/TPI; 3.1 months). Conclusions: Our study showed that REG and FTD/TPI led to prolongation of sOS in the real-world setting, indicating the importance of strategies which make all active agents available to pts with mCRC.

BRAF (V600E) mutant metastatic colorectal cancer: What is the role of the antiangiogenic therapy in a real-world setting?

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e15561-e15561
Author(s):  
Nieves Martinez Lago ◽  
Ana Fernandez Fernandez Montes ◽  
Marta Covela Rúa ◽  
Elena Brozos Vazquez ◽  
Juan Cruz De La Camara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Antiangiogenic Therapy ◽  
Braf V600e ◽  
Real World Setting

scholarly journals Efficacy of Dabrafenib Plus Trametinib Combination in Patients with BRAF V600E-Mutant NSCLC in Real-World Setting: GFPC 01-2019

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3608
Author(s):  
Jean-Bernard Auliac ◽  
Sophie Bayle ◽  
Pascal Do ◽  
Gwenaëlle Le Garff ◽  
Magali Roa ◽  
...  
Keyword(s):  
Real World ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Braf V600e ◽  
Efficacy And Safety ◽  
First Line ◽  
Multicentric Study ◽  
Free Survival ◽  
Entire Cohort ◽  
Real World Setting

Dabrafenib plus trametinib combination is approved in Europe for BRAF V600E-mutant metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to assess efficacy and safety of this combination in a real-world setting. This retrospective multicentric study included 40 patients with advanced NSCLC harboring BRAF V600E mutation and receiving dabrafenib plus trametinib. The median progression-free survival (PFS) and overall survival (OS) were 17.5 (95% CI 7.1–23.0) months and 25.5 (95% CI 16.6–not reached) months in the entire cohort, respectively. For the 9 patients with first-line treatment, median PFS was 16.8 (95% CI 6.1–23.2) months and median OS was 21.8 (95% CI 1.0–not reached) months; for the 31 patients with second-line or more treatments, median PFS and OS were 16.8 (95% CI 6.1–23.2) months and 25.5 (95% CI 16.6–not reached) months, respectively. Adverse events led to permanent discontinuation in 7 (18%) patients, treatment interruption in 8 (20%) and dose reduction in 12 (30%). In conclusion, these results suggest that efficacy and safety of dabrafenib plus trametinib combination in patients with BRAF V600E metastatic NSCLC are comparable in a real-world setting and in clinical trials for both previously untreated and treated patients.

scholarly journals KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 219 ◽  
Author(s):  
Nuria Garcia-Carbonero ◽  
Javier Martinez-Useros ◽  
Weiyao Li ◽  
Alberto Orta ◽  
Nuria Perez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Predictive Biomarkers ◽  
Braf V600e ◽  
Chemotherapy Response ◽  
First Line ◽  
Standard Chemotherapy ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Line Standard

KRAS mutation is a confirmed predictive biomarker for anti-EGFR monoclonal antibody therapy response for metastatic colorectal cancer. However, its prognosis impact and the predictive potential for first-line standard chemotherapy remains unclear. On the other hand, V600E mutation is the most frequent and studied mutation in the BRAF gene, and it has been associated with a poor outcome of patients and a low response to anti-EGFR treatment. Thus, the aim of this study is to evaluate the role of KRAS and BRAF mutations as prognosis factors and predictive biomarkers for 1st line standard chemotherapy in metastatic colorectal cancer. KRAS mutations and BRAF V600E mutations exhibited a poor outcome (p = 0.021 and p < 0.0001, respectively). Cox multivariate analysis showed that the presence of liver metastasis (HR = 1.595; 95% CI: 1.086–2.343; p = 0.017), KRAS mutation (HR = 1.643; 95% CI: 1.110–2.431; p = 0.013) and BRAF V600E mutation (HR = 5.861; 95% CI: 2.531–13.570; p < 0.0001) were statistically significant co-variables for progression-free survival. Interestingly, patients with KRAS mutations were associated with a poor response to first line standard chemotherapy (p = 0.008). In contrast, the BRAF V600E mutation did not have any impact on the first line standard chemotherapy response (p = 0.540). Therefore, in the present study, we provide new insight on the role of KRAS and BRAF, not only as prognosis biomarkers, but also as first line standard chemotherapy response biomarkers in metastatic colorectal cancer.

Assessing real-world outcomes in metastatic colorectal cancer with KRASG12C mutation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16072-e16072
Author(s):  
Hui-Li Wong ◽  
Wanyuan Cui ◽  
Matthew Loft ◽  
Margaret Lee ◽  
Rachel Wong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Features ◽  
Real World ◽  
Predictive Biomarker ◽  
Tumor Location ◽  
Prognostic Impact ◽  
Braf Mutations ◽  
Specific Targeting ◽  
Metastatic Sites

e16072 Background: The KRASG12C mutation is present in 3% of colorectal cancer and is of particular interest given the recent development of specific targeting drugs. Previous data suggest KRAS (all) mutations may impact prognosis. Here we assess the clinical features and outcomes of real world patients with KRASG12C mutant metastatic colorectal cancer (mCRC) to explore any clinicopathologic associations and prognostic impact. Methods: Patients diagnosed with mCRC between January 2011 and December 2018 were included in this prospective mCRC registry. Patients with BRAF mutations, unknown or unspecified KRAS variants were excluded. Clinicopathologic features, treatment and overall survival (OS) were compared for RAS wildtype (RASWT) and KRASG12C mutant patients, and between KRASG12C and other (RASother) mutations. Results: Of 1308 patients analysed, 674 (52%) were RASmut, of whom 56 (8.3%) were KRASG12C. More patients with KRASG12C were female compared to RASother and RASWT (Table). No differences were observed in primary tumor location, number of metastatic sites and distribution of metastases. The proportion of patients undergoing metastasectomy was similar between KRASG12C and RASother, and KRASG12C and RASWT. There was no difference in the proportion of patients receiving systemic therapy. RASWT patients received more lines of therapy. Median OS was similar between KRASG12C, RASother, and RASWT: 31.7 vs 29.2 vs 31.8 months respectively (P = 0.545). Conclusions: KRASG12C mutations were observed in 4.3% of mCRC patients and in 8.3% of RAS mutant cases. Patients with KRASG12C have comparable clinical features to RASWT or RASother mCRC. Treatment and survival were also similar between groups. KRASG12C does not appear to be prognostic, but may be an important predictive biomarker as promising targeted therapies continue to be developed. [Table: see text]

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