HER2 exon 20 insertion mutations in lung adenocarcinoma with leptomeningeal metastasis: a case report and response to poziotinib

Abstract

Leptomeningeal metastasis (LM) is associated with poor prognosis and represents a terminal event of non-small cell lung cancers (NSCLC). In previous studies, most of LM-patients have detected epidermal growth factor receptor (EGFR) mutation and responded to the third generation of EGFR-tyrosine kinase inhibitor (TKI). This study aimed to report a case of ERBB2 (HER2) exon 20 insertion mutations in the cerebrospinal fluid (CSF) of LM-patient which response to poziotinib. At the beginning, postoperative pathology showed a primary invasive adenocarcinoma with no mutations in EGFR and ROS-1. Pemetrexed plus carboplatin combined with bevacizumab was administered as the first-line followed by bevacizumab alone for continuation maintenance therapy. Targeted therapy and immunotherapy were given after the disease progressed in two months. Subsequently, the patient developed mental symptoms and adenocarcinoma cells were found in the CSF. Next-generation sequencing (NGS) results showed HER2 exon 20 insertion mutations in the primary tissue, CSF and plasma samples. Then, poziotinib was administered and the symptoms improved significantly after 3 days and the progress free survival was nearly 2 months. Therefore, we speculate that the CSF concentration and penetration rate of poziotinib may significantly higher than of other TKIs so that it achieves a higher CSF concentration than standard dosing, and successfully controlled LM. It may provide a new therapeutic option for LM-patient and may be especially who are lung adenocarcinoma with HER2 exon 20 insertion.

Different gene alterations in patients with non-small-cell lung cancer between the eastern and southern China

“…In the present study, it is worth noting that different ERBB2 20ins subtypes was identified in patients between the two regions. TKIs targeting ERBB2 have limited activity in patients with ERBB2 -positive tumors [ 37 , 38 ], although some case series have reported that lung cancer patients with ERBB2 20ins can benefit from TKIs, such as afatinib [ 39 ] and poziotinib [ 40 ]. However, response heterogeneity was observed in patients harboring different 20ins subtypes [ 39 , 41 ].…”

The Riddle of the Sphinx: Progress in Leptomeningeal Metastasis of Non–Small Cell Lung Cancer

“…Currently, there are relatively few reports of rare oncogenes, such as RET rearrangement or HER2 mutation causing LM. There is a case report 64 of lung adenocarcinoma accompanied by rare oncogene HER2 exon 20 insertion mutations that causes LM. After 3 days of administration of poziotinib, the symptoms improved significantly and the PFS was nearly 2 months.…”