Efficacy and tolerability of vemurafenib in BRAF-mutant acral and mucosal melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21017-e21017
Author(s):  
Xue Bai ◽  
Lu Si ◽  
Zhihong Chi ◽  
Xinan Sheng ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Survival Data ◽  
Survival Curve ◽  
Similar Efficacy ◽  
Mucosal Melanoma ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Efficacy And Safety ◽  
Hand Foot Syndrome ◽  
Braf Mutant

e21017 Background: Vemurafenib has substantially impressive clinical efficacy in cutaneous melanoma (CM). However, compared with their cutaneous counterpart, acral melanoma (AM) and mucosal melanoma (MM) have distinct genetic patterns and worse prognosis. The efficacy and safety profiles of vemurafenib in AM and mm remain unclear. Methods: Clinical, pathological, and therapeutic data were collected and reviewed of patients (pts) with metastatic or unresectable BRAF-mutant AM and mm hospitalized and administrated vemurafenib during January 2011 and January 2017. Responses were evaluated by RECIST v1.1, survival data were analyzed by Kaplan-Meier survival curve, and adverse effects were assessed by CTCAE v4.0. Results: 24 pts were identified, 13 (54.2%) with AM, 11 (45.8%) with mm (1 patient without available radiology data). All 13 AM pts harbored BRAF V600E mutation (1 with simultaneous C-KIT E861K mutation); 10/11 (90.9%) mm pts carried BRAF V600E mutation (1 with simultaneous PDGFRA V824I mutation), 1/11 (9.1%) had BRAF D594N mutation. Median PFS were 5.4 (95%CI 3.5-8.7) and 4.5 (95%CI 1.5-15.0) months, median OS were 11.7 (95%CI 8.1-23.6) and 7.9 (95%CI 4.6-26.2) months; ORRs were 61.5% (8/13) and 40.0% (4/10), DCRs were 92.3% (12/13) and 90.0% (9/10) in AM and MM, respectively. Vemurafenib was well tolerated. The most common adverse effects (AEs) were hand-foot syndrome in AM and elevation of total cholesterol in MM, with the incidence of 23.1% (3/13) and 18.2% (2/11), respectively. Grade 3/4 AEs have not been observed. No patient discontinued vemurafenib because of treatment related toxicity. Conclusions: Vemurafenib yields substantial response in pts with AM and MM. Compared with in CM, vemurafenib has similar efficacy and safety profiles in BRAF-mutant AM and MM.

scholarly journals A meta-analysis comparing regorafenib with TAS-102 for treating refractory metastatic colorectal cancer

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052092640
Author(s):  
Guan-Li Su ◽  
Yuan-Yuan Wang ◽  
Jin-Cheng Wang ◽  
Hao Liu
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Hand Foot Syndrome

Objective We performed this meta-analysis to compare the efficacy and toxicity of regorafenib and TAS-102. Methods Electronic databases were searched to identify studies comparing the efficacy and safety of regorafenib and TAS-102 in patients with chemotherapy-refractory metastatic colorectal cancer using pooled analyses. Results Three clinical trials were included in this analysis. Regarding the reasons for treatment discontinuation, regorafenib was significantly associated with disease progression (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.21–0.50) and adverse events (OR = 4.38, 95% CI = 2.69–7.13). However, overall (OR = 0.97, 95% CI = 0.81–1.17) and progression-free survival (OR = 1.01, 95% CI = 0.86–1.18) did not significantly differ between the groups. The most common treatment-related adverse events in the regorafenib group were neutropenia (OR = 0.06, 95% CI = 0.03–0.11), hand–foot syndrome (OR = 50.34, 95% CI = 10.44–242.84), and liver dysfunction (OR = 34.51, 95% CI = 8.30–143.43). Conversely, the incidence of thrombocytopenia did not differ between the two groups. Conclusions Regorafenib and TAS-102 have similar efficacy but different adverse event profiles. Differences in the toxicity profiles of the two drugs will help guide treatment selection.

Prognostic value of RAS, BRAF, and PIK3CA mutations in early-stage colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 594-594
Author(s):  
Jennifer Elizabeth Byer ◽  
Nishi Kothari ◽  
TzuHua Juan ◽  
Jamie K. Teer ◽  
Michael J. Schell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Data ◽  
Braf Mutation ◽  
Prognostic Value ◽  
Early Stage ◽  
Stage I ◽  
Braf V600e ◽  
Pik3ca Mutations ◽  
1000 Genomes ◽  
Braf Mutant

594 Background: Activating mutations in the KRAS, BRAF and PIK3CA oncogenes deregulate growth-factor pathways and promote metastasis in colorectal cancer (CRC). The prognostic value of these mutations has been reported with conflicting results in early CRC. We evaluated RAS, BRAF, and PIK3CA mutations as prognostic biomarkers in early stage (stage I-III) colorectal cancer (CRC) patients. Methods: Tumor samples collected from 302 early stage CRC patients diagnosed between 1998 and 2010 were analyzed as part of a multi-institutional observational study. Targeted exome sequencing was performed using the Illumina NGS platform with 50-100X coverage of mutations. The BWA/GATK pipeline was used to identify variants and indels. Matched normal samples were not available for comparison to identify somatic mutations, therefore 1000 Genomes was used to filter normal variants. Variants identified in 1000 Genomes with an MAF <0.01 were filtered. Overall survival data was collected via retrospective chart review. Extended RAS, BRAF V600E, and PIK3CA (exon 9 and 20) mutations were evaluated. The log-rank test was used to compare survival distributions. Results: 302 patients were eligible for analysis (53 stage I, 125 stage II, 124 stage III). 109 patients had RAS mutations (KRAS or NRAS), 41 patients had BRAF mutations, and 29 patients had PIK3CA mutations. Of the 247 patients with microsatellite stability (MSS) 98 were RAS mutant, 10 were BRAF mutant, and 19 were PIK3CA mutant. Of the 55 patients with microsatellite instability high (MSI-H) 11 were RAS mutant, 31 were BRAF mutant, and 10 were PIK3CA mutant. BRAF mutation was prognostic for decreased OS (p= 0.0245), particularly in patients with MSS tumors (p=0.0141). RAS and PIK3CA mutations did not have prognostic value for OS (p =0.72 and 0.23 respectively). Conclusions: In early stage colorectal cancer, we confirmed BRAF mutation is prognostic for OS particularly in MSS patients. RAS and PIK3CA mutations did not confer prognostic value.

Clinicopathologic features and impact of metastasectomy in patients with BRAF-mutant metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15547-e15547
Author(s):  
Jianwei Zhang ◽  
Cailu Shen ◽  
Jianxia Li ◽  
Zehua Wu ◽  
Huabin Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Systemic Treatment ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Clinicopathologic Features ◽  
Significant Difference ◽  
The Impact ◽  
Braf Mutant

e15547 Background: BRAF V600E mutation is associated with poor prognosis in patients with metastatic colorectal cancer (mCRC), while the non-V600E mutation mCRC patients showed better prognosis than that of V600E mutation. The clinicopathologic features between V600E and non-V600E mutation has not yet been fully evaluated. And the impact of metastasectomy for patients with BRAF-mutant mCRC was not well-known. Methods: A retrospective study was conducted to evaluate the clinical and pathological characteristics of patients with BRAF-mutant mCRC. Next generation sequencing (22-gene panel) was performed in some of the patients. Survival was also analyzed in the cohort of BRAF V600E and non-V600E mutation with or without metastasectomy. Results: Between December 2014 and August 2020, 116 patients with BRAF-mutant mCRC were enrolled, including 94 patients with BRAF V600E mutation and 22 patients with non-V600E mutation. Significant difference was observed in the prevalence of peritoneal metastasis (69.1% vs. 27.3%, P = 0.001) and lung metastasis (11.7% vs. 36.4%, P = 0.009) between BRAF V600E mutation and non-V600E mutations. In genomic profile, SMAD4 mutation (30.7% vs. 13.7%) showed higher prevalence in patients with BRAF V600E mutation than that of non-V600E mutations, while RAS mutation (18.2% vs. 6.4%) and FBXW7 mutation (13.7% vs 3.1%) had higher incidence in BRAF non-V600E mutations than that of V600E mutation. Patients with BRAF V600E mutation showed a poorer overall survival than those with non-V600E mutations (13.9 vs. 26.8 months, P = 0.038). Totally, 46 patients received metastasectomy after systemic treatment. The median survival for BRAF V600E patients with or without metastasectomy was not reach (42.3+ months) vs. 8.3 months, respectively ( P < 0.001), and for non-V600E patients with or without metastasectomy was not reach (64.2+ months) vs. 23.3 months, respectively (P < 0.001). In multivariate analysis, ECOG performance status (0-1 vs. 2) ( P = 0.001), Staging (IVa-b vs. IVc) ( P = 0.01) and metastasectomy ( P = 0.001) were independent prognostic factors of overall survival. Conclusions: BRAF V600E mutation defines a subgroup of mCRC with worse prognosis. Metastasectomy might improve the survival benefit in carefully selected BRAF-mutant mCRC patients after systemic treatment.

A screening test for BRAF mutant melanoma: Immunohistochemical (IHC) analysis of BRAF V600E mutation.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e21076-e21076
Author(s):  
Tomas Lyons ◽  
Odharnaith O'Brien ◽  
Sandra Murphy ◽  
Richard Bambury ◽  
Deirdre O'Mahony ◽  
...  
Keyword(s):  
Screening Test ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Braf Mutant

scholarly journals Blood-Based Detection of BRAF V600E in Gliomas and Brain Tumor Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1227
Author(s):  
Keiko M. Kang ◽  
Koushik Muralidharan ◽  
Anudeep Yekula ◽  
Julia L. Small ◽  
Zachary S. Rosh ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Tumor Metastasis ◽  
Disease Status ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Healthy Control ◽  
Small Patient ◽  
Hotspot Mutations ◽  
Braf Mutant

Liquid biopsy provides a minimally invasive platform for the detection of tumor-derived information, including hotspot mutations, such as BRAF V600E. In this study, we provide evidence of the technical development of a ddPCR assay for the detection of BRAF V600E mutations in the plasma of patients with glioma or brain metastasis. In a small patient cohort (n = 9, n = 5 BRAF V600E, n = 4 BRAF WT, n = 4 healthy control), we were able to detect the BRAF V600E mutation in the plasma of 4/5 patients with BRAF V600E-tissue confirmed mutant tumors, and none of the BRAF WT tumors. We also provide evidence in two metastatic patients with longitudinal monitoring, where the plasma-based BRAF V600E mutation correlated with clinical disease status. This proof of principle study demonstrates the potential of this assay to serve as an adjunctive tool for the detection, monitoring, and molecular characterization of BRAF mutant gliomas and brain metastasis.

scholarly journals LGG-05. GENERATION OF NOVEL MOUSE MODELS FOR BRAF V600E MUTANT GLIOMAGENESIS TO GAIN MECHANISTIC INSIGHTS INTO TUMOR FORMATION AND PROGRESSION

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i32-i32
Author(s):  
Claudia K. Petritsch ◽  
Anne Marie Barrette ◽  
Jong-Whi Park
Keyword(s):  
Mouse Models ◽  
Mutant Mouse ◽  
Tumor Formation ◽  
Genetically Engineered ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Common Mutation ◽  
Low Grade ◽  
Braf Mutant

Abstract Background The BRAF V600E mutation occurs in ~ twenty percent of histologically diverse pediatric gliomas and is the second most common mutation in pediatric low-grade gliomas (LGG). BRAF V600E expression in LGG with balanced CDKN2A is associated with a higher rate for progression than for BRAF V600E wildtype tumors, and despite adjuvant therapy, consisting of resection, radiation and chemotherapy. Progression invariably occurs in BRAF V600E mutant CDKN2A deleted gliomas, marking a high-risk group. Here, we aim to overcome the lack BRAF V600E mutant glioma models that allow for studies of stem and progenitor cells and the immune system ability to understand progression. Methods We develop novel immunocompetent, stem and progenitor cell-based mouse models for BRAF mutant gliomas, including genetically engineered mouse models (GEMMs), orthotopic glioma models derived from gliomas in GEMMs as well as in vitro models of those tumors. BRAF mutant mouse brains and cells were analyzed by immunofluorescence staining, flow cytometry, mass cytometry and RNA sequencing. Results Ongoing model development studies indicate that BRAF V600E mutant gliomas in murine brain exhibit very similar neuroanatomical preferences to human gliomas. The BRAF V600E mutation exacerbates the heterogenous cell cycling pattern of normal neural stem and progenitors and expands a symmetrically dividing progenitor population. Cellular plasticity rather than cellular lineage hierarchy drives the generation of a therapy resistant stem cell pool. Transcriptomic analyses of neuroglial stem cells with induced BRAF V600E expression provide insights into mechanisms for neoplastic transformation and progression. Conclusion Analyses of two independent BRAF V600E mutant mouse models provide novel insights into the role for tumor intrinsic factors, such as plasticity and stemness, and the tumor microenvironment in progression.

scholarly journals Efficacy and safety of bevacizumab in combination with irinotecan and capecitabine in first-line treatment of metastatic colorectal carcer

2017 ◽  
Vol 74 (3) ◽  
pp. 249-255
Author(s):  
Sasa Jungic ◽  
Biljana Tubic ◽  
Radoslav Gajanin ◽  
Zdenka Gojkovic ◽  
Ivanka Rakita
Keyword(s):  
Adverse Effects ◽  
Adverse Reactions ◽  
Progressive Disease ◽  
Overall Response Rate ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Hand Foot Syndrome ◽  
First Line Treatment

Background/Aim. The efficacy and safety of bevacizumab (BEV) in combination with capecitabin and irinotecan in first-line therapy for patients with metastatic colorectal cancer (mCRC) were studied. In order to improve safety and efficacy of chemotherapy, as well as to reduce adverse reactions to a minimum, doses of active agents applied were changed in relation to previously employed schedules. Methods. Patients with histologically documented mCRC with no previously received chemotherapy or with received adjuvant or neoadjuvant chemotherapy, which ended 6 months before capecitabin treatment (1000 mg/m2 per os from the 2nd to 8th day of each cycle), irinotecan (175 mg/m2 iv every 2 weeks), plus bevacizumab (5 mg/kg iv every 2 weeks) were observed. Results. This prospective study included 35 patients of both sexes. The overall response rate (ORR) of 28.6%, partial response (PR) of 28.6%, progressive disease (PD) of 28.6% and stable disease (SD) of 42.8% were found. The progressionfree survival (PFS) of the analyzed patients was 11.3 (95% CL: 9.1?12.9) months while overall survival (OS) of the included patients was 25.2 (95% CL: 17.4?28.4) months and 117 adverse effects were recorded in 24 patients. Alopecia, nausea and vomiting, hemorrhage, hand-foot syndrome, diarrhea, abdominal pain, proteinuria, and hypertension (51.4%, 37.1%, 37.1%, 25.7%, 22.8%, 20.0%, 20.0% and 17.1%, respectively) were most frequently observed adverse effects. Conclusion. The results of this clinical trial support and recommend the use of bevacizumab plus capecitabin and irinotecan in the doses and schedule applied throughout this study as the first-line treatment of mCRC patients.

scholarly journals BRAF-mutant melanoma of the skin during pregnancy with dichorionic diamniotic twins. Clinical case

MD-Onco ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 38-42
Author(s):  
M. M. Davydov ◽  
P. A. Zeynalova ◽  
A. A. Fedenko ◽  
D. A. Chekiny ◽  
E. K. Ibragimov ◽  
...  
Keyword(s):  
Lymph Node ◽  
Clinical Case ◽  
Retrospective Studies ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Malignant Neoplasms ◽  
Node Dissection ◽  
Child Bearing ◽  
Braf Mutant ◽  
Conclusive Data

Per the majority of authors, melanoma is the most common tumor diagnosed during pregnancy (31 % of all malignant neoplasms). In approximately 1/3 of women melanoma developed in child-bearing age is diagnosed during pregnancy or in the postpartum period. However, only some retrospective studies analyzed the effect of pregnancy on melanoma development, and conclusive data on development, progression and treatment of BRAF-mutant melanoma is lacking. In this subpopulation of patients, BRAF status supposedly can negatively affect disease outcome irrespective of treatment methods.The article presents a clinical case of recurrence of melanoma with the BRAF V600E mutation during pregnancy. The patient underwent lymph node dissection during pregnancy prolongation, after labor she received antitumor drug therapy with МЕК and ВRAF inhibitors. Melanoma recurrence during pregnancy did not worsen treatment outcomes for the mother and embryo.

Therapie des BRAF-mutierten NSCLC

2018 ◽  
Vol 09 (05) ◽  
pp. 239-239
Author(s):  
Dr. Susanne Krome
Keyword(s):  
Phase Ii ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Alk Rearrangement

BRAF-mutierte nicht kleinzellige Bronchialkarzinome (NSCLC) sind besonders aggressiv. Gezielte Antikörpertherapien verbesserten die Behandlungsergebnisse. Bei einem ALK-Rearrangement ging eine lange progressionsfreie Zeit nicht zu Lasten der Post-Progressionsphase. Die Sekundäranalyse einer nicht randomisierten Phase-II-Studie zeigt dies nun auch für Patienten mit einer BRAF-V600E-Mutation.

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