Successful tepotinib treatment of adenocarcinoma with MET exon 14 skipping and discordant results between Oncomine Dx target test and ArcherMET: A case report

Abstract

Patients with non-small cell lung cancer (NSCLC) are often positive for oncogenic driver mutations, such as EGFR, ALK, BRAF, RET and MET exon 14 skipping mutations (METex14 skipping). Recently, METex14 skipping has become a functional biomarker for NSCLC with the approval of MET kinase inhibitors. Tepotinib is an oral MET kinase inhibitor. Its overall response rate is 46%, and the median duration of the response is 11.1 months. In Japan, companion diagnostics for tepotinib are limited with the ArcherMET and AmoyDx test, but not with Oncomine Dx target test. The present study reports the case of a 60-year-old male patient with lung adenocarcinoma harboring METex14 skipping, which was positive on Oncomine DxTT, but not on ArcherMET. In his sample used for Oncomine DxTT, the read count of MET(13)-MET(15) products was only 46. He was treated with various chemotherapeutic agents, but developed cardiac tamponade due to the progression of the disease of mediastinal lymph node metastases. Tepotinib was administered following pericardial drainage, resulting in an immediate response in all lesions. The majority of the discordant samples between Oncomine DxTT and ArcherMET had read counts <800, and the patient described herein had only 46. Therefore, the results of the present study indicate that the use of tepotinib should be considered even in patients whose METex14 skipping results were negative with ArcherMET, yet positive on Oncomine DxTT, particularly relatively with low lead counts.

Retrospective Analysis to Optimize the Detection of MET Exon 14 Skipping Mutations in Non-Small Cell Lung Cancer

“…Recently, accompanied by the tyrosine kinase inhibitors developed and applied in clinical treatment, companion diagnostics (CDx) kits were acquired to monitor and evaluate their treatment efficacy. Based on this purpose, several CDx have been developed to assess the treatment efficacy of these anticancer medication, such as FoundationOne ™ [5,6] (Roche, Basel, Switzerland), ArcherMET ™ [7,8] (Invitae, San Francisco, CA, USA), or Oncomine ™ Focus Assay (Thermo Fisher Scientific, Waltham, MA, USA) [9,10]. Each CDx were developed by different strategies and are run on various NGS platforms, such as FoundationOne ™ is designed to detect 324 potential cancer-related Diagnostics 2024, 14, 1110 2 of 7 genes through the Illumina ® platform.…”

“…Since our hospital uses similar strategies for MET ex14 detection, it is possible that false-positive results have been reported for our patients, and it is crucial to assess our detection methods for MET ex14. This study evaluated all positive cases tested using OFA and compared the results with those of the Pan Lung Cancer PCR Panel (AmoyDx ® , Xiamen, China) [ 8 ] and reverse transcription (RT)-PCR to optimize the routine testing for MET ex14.…”