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

Abstract

<i>BRAF</i> mutations, primarily sensitizing mutations, such as <i>BRAF^V600E</i> , have been proven to response to the <i>BRAF</i> 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 <i>BRAF^S365L</i> mutation (a rare mutation following <i>BRAF^V600E</i> -inhibitor treatment) in NSCLC is unknown. Vemurafenib, another <i>BRAF</i> inhibitor, can reverse the resistance that develops with the <i>BRAF^S365L</i> 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 <i>BRAF^V600E</i> mutation who benefited from dabrafenib combined with trametinib, and following the development of the <i>BRAF^S365L</i> 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.