Reference Detail

Ref Type

PMID

(34178685)

Authors

Jiang J, Gao J, Wang G, Lv J, Chen W, Ben J, Wang R

Title

Case Report: Vemurafenib Treatment in Brain Metastases of BRAFS365L -Mutant Lung Papillary Cancer by Genetic Sequencing of Cerebrospinal Fluid Circulating Tumor DNA Detection.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Frontiers in oncology	11		2021	688200	Front Oncol

URL

Abstract Text

BRAF mutations, primarily sensitizing mutations, such as BRAFV600E , have been proven to response to the BRAF inhibitor, Dabrafenib combined with trametinib therapy, but there have been no data demonstrating that it has activity against NSCLC-related brain metastases (BM). How patients harboring BRAFS365L mutation (a rare mutation following BRAFV600E -inhibitor treatment) in NSCLC is unknown. Vemurafenib, another BRAF inhibitor, can reverse the resistance that develops with the BRAFS365L mutation following dabrafenib combined with trametentinib treatment in melanoma, but none has been reported in NSCLC. Lung papillary cancer, as a rare typing, occupies about 4% of NSCLC. Hence, we reported the first case of a patient with BM of lung papillary carcinoma harboring a BRAFV600E mutation who benefited from dabrafenib combined with trametinib, and following the development of the BRAFS365L mutation, vemurafenib remained an effective therapeutic option. Moreover, we found that the next-generation sequencing (NGS) of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) may potentially provide more accurate information about intracranial lesions than ctDNA in the blood serum, which will be a better detection method.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
BRAF	S365L	missense	unknown	BRAF S365L does not lie within any known functional domains of the Braf protein (UniProt.org). S365L has been demonstrated to occur as a secondary drug resistance mutation (PMID: 34178685), but has not been biochemically characterized and therefore, it's effect on Braf protein function is unknown (PubMed, May 2024).	Y

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	lung papillary adenocarcinoma	predicted - sensitive	Dabrafenib + Trametinib	Case Reports/Case Series	Actionable	In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in regression of the lesions in the chest, abdomen and brain in a patient with lung papillary carcinoma harboring BRAF V600E but progression was observed 3 months later (PMID: 34178685).	34178685
BRAF S365L BRAF V600E	lung papillary adenocarcinoma	predicted - sensitive	Bevacizumab + Vemurafenib	Case Reports/Case Series	Actionable	In a clinical case study, Zelboraf (vemurafenib) and Avastin (bevacizumab) combination treatment resulted in regression of some brain lesions while others remained stable in a patient with lung papillary carcinoma harboring BRAF V600E and S365L (PMID: 34178685).	34178685
BRAF S365L BRAF V600E	lung papillary adenocarcinoma	predicted - resistant	Dabrafenib + Trametinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung papillary carcinoma harboring BRAF V600E who previously responded to Tafinlar (dabrafenib) and Mekinist (trametinib) treatment was found to have acquired BRAF S365L upon disease progression (PMID: 34178685).	34178685