AUTHOR=Chou Yun-Tse , Lin Chien-Chung , Lee Chung-Ta , Pavlick Dean C. , Su Po-Lan 

TITLE=Durable Response of Dabrafenib, Trametinib, and Capmatinib in an NSCLC Patient With Co-Existing BRAF-KIAA1549 Fusion and MET Amplification: A Case Report

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.838798

DOI=10.3389/fonc.2022.838798

ISSN=2234-943X

ABSTRACT=<p><italic>BRAF</italic> fusions are rare driver oncogenes in non-small cell lung cancer (NSCLC). Similar with <italic>BRAF</italic> V600E mutation, it could also activate the MAPK signaling pathway. There are a few case reports which had indicated the potential response to BRAF inhibitors and its important role as <italic>de novo</italic> driver mutation. In addition, the co-occurring <italic>MET</italic> amplification has been defined as a poor prognostic factor in patients with epidermal growth factor receptor (<italic>EGFR</italic>) mutant NSCLC. Currently, there are ongoing clinical trials which investigate the <italic>MET</italic> amplification as a therapeutic target in patients with <italic>EGFR</italic> mutant NSCLC and acquired resistance to osimertinib, which imply that the <italic>MET</italic> amplification also had a therapeutic significance. However, the co-occurring <italic>MET</italic> amplification had not been studied in patients with <italic>BRAF</italic> fusion before. A 67-year-old man was diagnosed with metastatic poorly-differentiated adenocarcinoma. He received first-line therapy with the combination of pembrolizumab and chemotherapy because the genomic test revealed wild-type <italic>EGFR</italic>, and negativity of ALK and ROS1 by immunohistochemical stain. Upon disease progression, the next-generation sequencing revealed co-occurring <italic>KIAA1549-BRAF</italic> fusion and <italic>MET</italic> amplification. Subsequent dabrafenib, trametinib, and capmatinib combination therapy showed a remarkable treatment effect. The combination therapy targeting the co-occurring driver mutations is a potential effective treatment for NSCLC patients. Further prospective study is still warranted to investigate the role of co-occurring driver mutations and the relevant treatment strategy.</p>