scholarly journals Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor–Refractory Metastatic Melanoma

JAMA Oncology ◽  
2016 ◽  
Vol 2 (8) ◽  
pp. 1056 ◽  
Author(s):  
Guo Chen ◽  
Jennifer L. McQuade ◽  
David J. Panka ◽  
Courtney W. Hudgens ◽  
Ali Amin-Mansour ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Combination Treatment ◽  
Braf Inhibitor

scholarly journals Encorafenib (Braftovi) in Combination With Binimetinib (Mektovi)

2021 ◽  
Vol 1 (7) ◽  
Author(s):  
Reimbursement Team
Keyword(s):  
Metastatic Melanoma ◽  
Gene Mutation ◽  
Combination Treatment ◽  
Braf Inhibitor ◽  
Previous Treatment ◽  
Mek Inhibitor ◽  
Toxicity Profile ◽  
First Line ◽  
Braf V600 Mutation ◽  
Public Drug

CADTH recommends that Braftovi in combination with Mektovi should be reimbursed by public drug plans for the treatment of unresectable or metastatic melanoma with a BRAF V600 mutation if certain conditions are met. Braftovi and Mektovi should only be reimbursed if used in combination and prescribed and monitored by clinicians with expertise in diagnosis and management of melanoma who are familiar with the toxicity profile associated with the Braftovi with Mektovi regimen and if it does not cost more than the least costly BRAF inhibitor and MEK inhibitor (BRAFi/MEKi) combination treatment. Braftovi with Mektovi should only be covered to treat adult patients with advanced or metastatic melanoma who have a BRAF V600 gene mutation that has been identified through a validated test. Patients who have not received previous treatment and patients whose disease has progressed after first-line immunotherapy are eligible for coverage.

scholarly journals Deregulated FASN Expression in BRAF Inhibitor-Resistant Melanoma Cells Unveils New Targets for Drug Combinations

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2284
Author(s):  
Serena Stamatakos ◽  
Giovanni Luca Beretta ◽  
Elisabetta Vergani ◽  
Matteo Dugo ◽  
Cristina Corno ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Metastatic Melanoma ◽  
Mutant Cell ◽  
Braf Inhibitor ◽  
Cancer Cell Line ◽  
Melanoma Cells ◽  
Melanoma Progression ◽  
Increased Sensitivity ◽  
Resistant Cells

Metabolic changes promoting cell survival are involved in metastatic melanoma progression and in the development of drug resistance. In BRAF-inhibitor resistant melanoma cells, we explored the role of FASN, an enzyme involved in lipogenesis overexpressed in metastatic melanoma. Resistant melanoma cells displaying enhanced migratory and pro-invasive abilities increased sensitivity to the BRAF inhibitor PLX4032 upon the molecular targeting of FASN and upon treatment with the FASN inhibitor orlistat. This behavior was associated with a marked apoptosis and caspase 3/7 activation observed for the drug combination. The expression of FASN was found to be inversely associated with drug resistance in BRAF-mutant cell lines, both in a set of six resistant/sensitive matched lines and in the Cancer Cell Line Encyclopedia. A favorable drug interaction in resistant cells was also observed with U18666 A inhibiting DHCR24, which increased upon FASN targeting. The simultaneous combination of the two inhibitors showed a synergistic interaction with PLX4032 in resistant cells. In conclusion, FASN plays a role in BRAF-mutated melanoma progression, thereby creating novel therapeutic opportunities for the treatment of melanoma.

scholarly journals Isolation of extracellular vesicles improves the detection of mutant DNA from plasma of metastatic melanoma patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Davide Zocco ◽  
Simona Bernardi ◽  
Mauro Novelli ◽  
Chiara Astrua ◽  
Paolo Fava ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Braf Inhibitor ◽  
Extracellular Vesicle ◽  
Therapeutic Monitoring ◽  
Clinical Samples ◽  
Outer Side ◽  
Alternative Source ◽  
Gene Copies ◽  
Melanoma Patients ◽  
Promising Source

Abstract Detection of BRAFV600E within cell free tumor DNA (ctDNA) is emerging as a promising means to improve patients’ stratification or enable BRAF inhibitor (BRAFi) therapeutic monitoring in a minimally invasive manner. Here, we investigated whether extracellular vesicle-(EV)-associated-DNA (EV-DNA) has value as an alternative source of circulating BRAFV600E. To do so, we identified a clinical practice-compatible protocol for the isolation of EV-DNA and assessed BRAF gene status on plasma samples from metastatic melanoma patients at the beginning and during BRAFi therapy. This protocol uses a peptide with high affinity for EVs and it has been found to recover more mutant DNA from plasma than standard ultracentrifugation. Molecular analyses revealed that mutant DNA is largely unprotected from nuclease digestion, interacting with the outer side of the EV membrane or directly with the peptide. When used on clinical samples, we found that the protocol improves the detection of BRAFV600E gene copies in comparison to the reference protocol for ctDNA isolation. Taken together, these findings indicate that EVs are a promising source of mutant DNA and should be considered for the development of next-generation liquid biopsy approaches.

BRAF Inhibitor Resistance Mechanisms in Metastatic Melanoma: Spectrum and Clinical Impact

2014 ◽  
Vol 20 (7) ◽  
pp. 1965-1977 ◽  
Author(s):  
Helen Rizos ◽  
Alexander M. Menzies ◽  
Gulietta M. Pupo ◽  
Matteo S. Carlino ◽  
Carina Fung ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Braf Inhibitor ◽  
Resistance Mechanisms ◽  
Clinical Impact ◽  
Inhibitor Resistance

Panniculitis With Necrotizing Granulomata in a Patient on BRAF Inhibitor (Dabrafenib) Therapy for Metastatic Melanoma

2015 ◽  
Vol 37 (8) ◽  
pp. e96-e99 ◽  
Author(s):  
Nisha S. Ramani ◽  
Jonathan L. Curry ◽  
Jyoti Kapil ◽  
Ronald P. Rapini ◽  
Michael T. Tetzlaff ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Braf Inhibitor

BRAF inhibitor activity in V600R metastatic melanoma – Response

2013 ◽  
Vol 49 (7) ◽  
pp. 1797-1798 ◽  
Author(s):  
Oliver Klein ◽  
Arthur Clements ◽  
Alexander M. Menzies ◽  
Sandra O’Toole ◽  
Richard F. Kefford ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Braf Inhibitor ◽  
Inhibitor Activity

Partial response of metastatic melanoma to BRAF-inhibitor-monotherapy in a pregnant patient with no fetal toxicity

2019 ◽  
Vol 29 (4) ◽  
pp. 446-447 ◽  
Author(s):  
Diane Marcé ◽  
Hélène Cornillier ◽  
Christelle Denis ◽  
Annie-Pierre Jonville-Bera ◽  
Laurent Machet
Keyword(s):  
Partial Response ◽  
Metastatic Melanoma ◽  
Braf Inhibitor ◽  
Pregnant Patient ◽  
Fetal Toxicity

scholarly journals Response to Ipilimumab/Nivolumab Rechallenge and BRAF Inhibitor/MEK Inhibitor Rechallenge in a Patient with Advanced Metastatic Melanoma Previously Treated with BRAF Targeted Therapy and Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Caitlyn N. Myrdal ◽  
Srinath Sundararajan
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Optimal Sequencing ◽  
The Right

Little is known about the optimal sequencing of targeted therapy and immunotherapy in the treatment of patients with BRAFV600-mutated metastatic melanoma. BRAF/MEK inhibition often has the benefit of rapid disease regression; however, resistance is frequently seen with long-term use. Treatment with immune checkpoint inhibitors offers the potential for long-term response but displays a lower rate of objective response. The benefit of synergy between therapies is apparent; however, there is limited data regarding optimal sequencing in the treatment of advanced melanoma. We present the case of a 62-year-old gentleman with advanced BRAFV600-mutated melanoma who followed an unconventional treatment path. After progressing on single-agent vemurafenib, he had response to multiple modalities of immunotherapy before progression. After, he had a substantial response to multiple BRAF/MEK inhibitor rechallenges before developing resistance. The patient is now stable after a retrial of combination immunotherapy. Our case illustrates that with the right sequencing of therapy, meaningful clinical responses can be elicited with rechallenging of targeted therapy and immunotherapy in metastatic melanoma.

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