Braf v600 mutation profile of metastatic melanoma in the thrace region of turkey

e20002 Background: Vemurafenib, a selective BRAF kinase inhibitor, is a new medicine against carcinoma.This work will discuss new approaches to the treatment of patients with metastatic melanoma, who have been proved to have BRAF V600 mutation. Methods: The 62-year-old patient was initially diagnosed in 2002 when the excision of melanoma of the left calf was performed. HP was Melanoma invasivum nodular, Breslow III, Clark IV, p T3, without angioinvasion. The stadium of illness was M1a (AJCC). Afterwards, she was operated four times. Chemyotherapy was performed with DTIC and in the further treatment secundary HT VLB-BLM-CDDP. In June 2012 the examination of the control ultrasound of the abdomen and pelvis registered the progression of illness. The liver indicated multiple changes of seundary deposit type, the largest of which was 24mm parailiac left lgl 53mm, inguinal left 23mm. It was confirmed that the patient had the mutation on the BRAF gene and she was included in the clinical study in the illness stadium M1c (AJCC). Subsequently the therapy with vemurafenib 960 mg twice a day was introduced, after which side effects were registered: rash gr. 2, arthralgia gr. 1 (pain in the hand joints) and the swelling of ankle joints gr. 1. The patient continued the vemurafenib therapy. At the latest examination in October 2012, the control CT screening registered the regression of secundary deposit by 40%. Results: Identifying the significance of BRAF has led to the development of numerous new medicines against carcinoma. One of them is vemurafenib (PLKS4032), a medicine inhibiting particularly BRAF V600 mutation. Stage I of studying this medicine showed a complete or partial tumor regression in 81% patients with V600 BRAF mutation, while stage showed a relative reduction of death risk in 63% patients, as well as a relative reduction of tumor progression risk in 74% patients in comparison to dakarbazin. Still, patients who take vemurafenib develop resistance to this medicine within 7 months on average. Conclusions: The development of vemurafenib and the role of BRAF targeted therapy in the treatment of metastatic melanoma ensure a new basis for the clinical research. Further clinical studies will research complex molecular mechanisms underlying resistance and toxicity to vemurafenib.

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The impact of BRAF mutation status on clinical outcomes with single-agent PD-1 inhibitor versus combination ipilimumab/nivolumab.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.10024 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 10024-10024

Author(s):

Vincent The-Luc Ma ◽

Stephanie Daignault ◽

Jessica Waninger ◽

Leslie Anne Fecher ◽

Michael Green ◽

...

Keyword(s):

Metastatic Melanoma ◽

Retrospective Analysis ◽

Braf Mutation ◽

Univariate Analysis ◽

Single Agent ◽

Mutation Status ◽

Melanoma Patients ◽

The Impact ◽

Braf Mutant ◽

Braf V600 Mutation

10024 Background: Nearly half of all metastatic melanoma patients possess the BRAF V600 mutation. Several therapies are approved for BRAF mutant metastatic melanoma, but it is unclear if there is a differential outcome to various immunotherapy regimens. Our aim was to better assess if BRAF mutation status has any impact on survival to combination ipilimumab/nivolumab (I/N) versus single-agent PD-1 inhibitor (PD-1i). Methods: We performed a single center, retrospective analysis on a cohort of patients diagnosed with metastatic or unresectable melanoma from 2012 to 2019 at the University of Michigan who were treated with standard I/N or PD-1i (nivolumab or pembrolizumab). A univariate analysis of progression free survival (PFS) and overall survival (OS) was stratified by treatment type and BRAF mutation status. A multivariate Cox regression of survival was used to compare the effects of the treatment groups adjusted by BRAF status, age, gender, pre-treatment LDH level, prior treatment status, and brain metastases status. Results: 323 patients were identified. 132 had BRAF V600 mutation and 191 had BRAF wildtype (WT) status. 138 patients received I/N and 185 patients received PD-1i. In our univariate analysis, there was no difference in PFS [HR: 0.72, 95% CI, 0.46 – 1.13] or OS [HR: 0.78, 0.44 – 1.38] with I/N versus PD-1i in the BRAF mutant cohort, but there was improved PFS [HR: 0.55, 0.35 – 0.88) and OS [HR: 0.52, 0.28 – 0.95] with I/N compared to PD-1i in the BRAF WT group. In the multivariate analysis, the BRAF WT group continued to show PFS benefit with I/N compared to PD-1i [HR: 0.57, 95% CI, 0.35 – 0.95], but the OS benefit no longer achieved statistical significance [HR: 0.54, 0.28 – 1.03]. Conclusions: Our study results were discordant with the observation in the landmark CheckMate 067 trial, which noted improved PFS and OS with I/N compared to nivolumab alone in the BRAF mutant group and no difference in the BRAF WT group. In our real-world retrospective analysis, I/N over PD-1i should be considered as initial immunotherapy for metastatic melanoma patients regardless of BRAF mutation status, but even more favorably in BRAF WT.

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Comparison of different testing methods for detection of BRAF V600 mutation in metastatic melanoma

Annals of Oncology ◽

10.1093/annonc/mdy047.072 ◽

2018 ◽

Vol 29 ◽

pp. iii28

Author(s):

J. Hernandez-Losa ◽

Y. Ruano ◽

I. Trigo Sanchez ◽

R. Somoza ◽

B. Ferrer ◽

...

Keyword(s):

Metastatic Melanoma ◽

Testing Methods ◽

Braf V600 Mutation

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503 BRAF-V600 Mutation discordance in Primary and Metastatic Melanoma

Journal of Investigative Dermatology ◽

10.1016/j.jid.2016.06.525 ◽

2016 ◽

Vol 136 (9) ◽

pp. S246

Author(s):

C. Martorelli ◽

C. Pellegrini ◽

L. Di Nardo ◽

A. Marinucci ◽

A. Antonini ◽

...

Keyword(s):

Metastatic Melanoma ◽

Braf V600 Mutation

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Low Incidence of Minor BRAF V600 Mutation-Positive Subclones in Primary and Metastatic Melanoma Determined by Sensitive and Quantitative Real-Time PCR

Journal of Molecular Diagnostics ◽

10.1016/j.jmoldx.2012.12.003 ◽

2013 ◽

Vol 15 (3) ◽

pp. 355-361 ◽

Cited By ~ 8

Author(s):

Thomas Kristensen ◽

Ole Clemmensen ◽

Lise Hoejberg

Keyword(s):

Metastatic Melanoma ◽

Real Time ◽

Real Time Pcr ◽

Quantitative Real Time Pcr ◽

Low Incidence ◽

Braf V600 Mutation

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Association of concomitant use of acid reducing agents in full-dose vemurafenib users with risk of progression in BRAF V600 mutation-positive unresectable or metastatic melanoma patients: A retrospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9540 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9540-9540

Author(s):

Lotte Marieke Knapen ◽

Rutger H.T. Koornstra ◽

Johanna H.M. Driessen ◽

Bas Van Vlijmen ◽

Sander Croes ◽

...

Keyword(s):

Cohort Study ◽

Metastatic Melanoma ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

First Line ◽

Full Dose ◽

Reduced Dose ◽

Increased Risk ◽

Risk Of Progression ◽

Braf V600 Mutation

9540 Background: Vemurafenib is used for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. The approved fixed vemurafenib dose of 960 mg twice daily may result in overexposure. Concomitant use of acid reducing agents (ARAs) may result in underexposure. Both situations are likely to affect treatment outcome. Therefore, the aim of this study was to determine the association between the use of vemurafenib (full-dose versus reduced dose) and/or concomitant ARA use (yes versus no) and the risk of disease progression. Methods: A retrospective cohort study was conducted using data from the electronic health record software of the Radboudumc pharmacy and medical records of the Radboudumc (March 17th 2012 to March 17th 2016). Patients (N = 112) using vemurafenib as first line treatment for melanoma were included. Multivariable cox regression estimated adjusted hazard ratios (HRa) and 95% confidence intervals (CI) of progression in vemurafenib users (full-dose N = 67 versus reduced dose N = 45) and/or concomitant ARA users (N = 38). Adjustments were made for age and sex. Results: The mean follow-up time was 3.5 months and 41 patients (36.6%) developed progression on first line vemurafenib. Co-treatment of ARAs in patients using full-dose vemurafenib was associated with a 4.6-fold increased risk of progression (HRa 4.56; 95% CI 1.51-13.75) as compared to full-dose vemurafenib users not co-treated with ARAs. No increased risk was found for users of vemurafenib in a reduced dose, regardless of concomitant ARA use. Conclusions: Concomitant use of ARAs in full-dose vemurafenib users was associated with an increased risk of progression. Physicians should be cautious to prescribe ARAs to patients tolerating full-dose vemurafenib. The presence of considerable confounding by disease severity, the small number of events and the hypothesis generating character of this study emphasize the need to prospective validate these results.

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