scholarly journals Urgent treatment of patients with metastatic melanoma using braf inhibitors in the absence of braf mutation status

2013 ◽  
Vol 24 (6) ◽  
pp. 1712-1713 ◽  
Author(s):  
P. Nathan ◽  
A. Sharma ◽  
P. Lorigan
Keyword(s):  
Metastatic Melanoma ◽  
Braf Mutation ◽  
Braf Inhibitors ◽  
Mutation Status

A phase III trial of nab-paclitaxel versus dacarbazine in chemotherapy-naive patients with metastatic melanoma: A subanalysis based on BRAF status.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9030-9030 ◽  
Author(s):  
Evan Hersh ◽  
Michele Del Vecchio ◽  
Michael Paul Brown ◽  
Richard Kefford ◽  
Carmen Loquai ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Braf Mutation ◽  
Performance Status ◽  
Braf Inhibitor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Mutation Status ◽  
Phase Iii Trial

9030 Background: Activating mutations of BRAF V600 can be found in 40%-50% of melanomas and are related to poor prognosis. In a phase 3 trial for the treatment of metastatic melanoma (MM) in chemotherapy-naive patients, nab-paclitaxel (nab-P) vs dacarbazine (DTIC) demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), assessed by independent radiological review (IRR), and a trend toward prolonged overall survival (OS) at the interim survival analysis. The study also explored the effect of BRAF status on the efficacy parameters. Methods: Chemotherapy-naive patients with stage IV melanoma (M1c stage 65%; elevated LDH 28%) and ECOG performance status 0-1 were randomized to nab-P 150 mg/m2 on days 1, 8, and 15 of a 28-day cycle (n = 264) or DTIC 1000 mg/m2 on day 1 of each 21-day cycle (n = 265) independent of BRAF status. Prespecified subgroup analyses of final PFS and interim OS in subgroups by BRAF status (V600E mutant, wild-type, or unknown) were performed. Results: BRAF mutation status was balanced between the treatment arms, with 36% and 38% of patients with known BRAF mutation status in the nab-P and DTIC arms, respectively. Patient characteristics were also balanced within BRAF subgroups. As shown in the Table, advantage in the nab-P arm vs DTIC arm was observed for both PFS and interim OS regardless of BRAFmutation status. Poststudy BRAF inhibitor treatment was also balanced. Conclusions: In this phase III trial, treatment effect was independent of BRAF mutation status, benefiting all patients who received nab-P vs DTIC. Therefore nab-P should be considered in the armamentarium for all chemotherapy-naive patients with MM. Clinical trial information: NCT00864253. [Table: see text]

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

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.

Impact of BRAF mutation and effectiveness of BRAF inhibitor on the brain metastases in patients with metastatic melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9048-9048
Author(s):  
Tulasi Gummadi ◽  
Roxana Stefania Dronca ◽  
Chul Kim ◽  
Lisa A. Kottschade ◽  
Rajendar K Mittapalli ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Retrospective Analysis ◽  
Braf Mutation ◽  
Braf Inhibitor ◽  
Preclinical Studies ◽  
Braf Inhibitors ◽  
Intracranial Disease ◽  
Extracranial Disease ◽  
The Brain

9048 Background: Brain metastases continue to be the major cause of morbidity and mortality in patients with metastatic melanoma. The impact of BRAF mutations and effectiveness of BRAF inhibitors on the brain metastases in these patients is lacking. Methods: Preclinical studies were conducted to assessthe steady-state brain and plasma distribution of vemurafenib, a BRAF inhibitor in FVB wild-type and Mdr1a/b-/-Bcrp1-/- mice deficient in the drug efflux transporters, p-glycoprotein (P-gp) and breast cancer resistant protein (BCRP). A retrospective analysis of patients with metastatic melanoma treated at University of Minnesota from August 2011 to December 2012 was conducted. A similar analysis of cases treated at Mayo Clinic is underway. Results: The preclinical studies in mice show that both P-gp and BCRP play a significant role in limiting the brain distribution of vemurafenib. Retrospective analysis was performed on 57 patients with Stage IIIc /IV cutaneous and mucosal melanoma. Patients with BRAF mutation had a higher incidence rate of brain metastases compared to patients without BRAF mutation, although it was not statistically significant (Incidence ratio=1.56; 95% CI=0.70-3.48; P=0.27). Vemurafenib neither reduced the incidence of brain metastases (Incidence ratio = 0.89; 95% CI: 0.30-2.60; P=0.83) nor made significant difference in overall survival. It was observed that treatment with BRAF inhibitor led to improvement in extracranial disease but did not affect progression of intracranial disease. Conclusions: In concordance with preclinical data which indicates that P-gp and BCRP play a significant role in limiting the brain distribution of vemurafenib, the retrospective analysis shows that there is improvement in extracranial disease but progression in intracranial disease with treatment with BRAF inhibitor in patients with metastatic malignant melanoma with BRAF mutation. Development of BRAF inhibitors that are not substrates for P-gp and BCRP or concomitant use of P-gp and BCRP inhibitors with vemurafenib, may be needed in order to control or prevent intracranial disease in these patients. Further analysis to improve statistical power of our observation is underway.

Clinical significance of BRAF mutation status in circulating tumor DNA of metastatic melanoma patients at baseline

2016 ◽  
Vol 25 (10) ◽  
pp. 783-788 ◽  
Author(s):  
Anne C. Knol ◽  
Audrey Vallée ◽  
Guillaume Herbreteau ◽  
Jean-Michel Nguyen ◽  
Emilie Varey ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Clinical Significance ◽  
Braf Mutation ◽  
Circulating Tumor Dna ◽  
Mutation Status ◽  
Melanoma Patients ◽  
Tumor Dna

Clinico-pathologic correlates of BRAF mutation status in 207 consecutive patients with metastatic melanoma.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 8548-8548 ◽  
Author(s):  
G. V. Long ◽  
A. M. Menzies ◽  
A. Nagrial ◽  
L. Haydu ◽  
A. L. Hamilton ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Braf Mutation ◽  
Mutation Status

scholarly journals P.141 Does BRAF mutation status or being on systemic therapy alter the radiological appearance of brain metastases in metastatic melanoma?

2021 ◽  
Vol 48 (s3) ◽  
pp. S60-S60
Author(s):  
O Hashmi ◽  
H Younus
Keyword(s):  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Braf Mutation ◽  
Imaging Features ◽  
Inclusion Criteria ◽  
Mutation Status ◽  
Magnetic Resonance Imaging Mri ◽  
Future Management

Background: The aim of this study is to investigate the differences in the radiological appearances of brain metastases (BM) in metastatic melanoma (MM) relative to BRAF mutation status. As well as to compare imaging differences in BM that occur prior to starting and during systemic therapy. Methods: A retrospective study was done over a 5 year period. Patients with MM with BM and known BRAF status were identified. 38 met the inclusion criteria. Imaging features on both Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) were reviewed. Results: Irrespective of BRAF mutation status, BM in MM tended to have a peripheral location with 30/38 cases having BM in the cerebral cortex. BRAF positive MM had a higher frequency of irregularly enhancing BM on CT and higher occurrence of BM showing high T1 signal on MRI. BM found during systemic treatment, regardless of BRAF status, showed less surrounding oedema, were smaller and harder to spot on CT. Conclusions: Understanding imaging features based on genetics could inform future management. The subtle features of BM on CT during systemic therapy means careful follow up with MRI may be indicated to confirm the diagnosis and to more accurately assess the burden of brain disease.

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