ctDNA dynamics, prognostic markers, and mechanisms of resistance in tepotinib-treated MET exon 14 (METex14) skipping NSCLC in the VISION trial Meeting Abstract

  


Authors: Xiuning, L.; Garassino, M. C.; Ahn, M . J.; Felip, E.; Cortot, A. B.; Hiroshi, S.; Mazières, J.; Thomas, M.; Viteri, S.; Conte, P.; Chih-Hsin Yang, J.; Iams, W. T.; Griesinger, F.; Braggio, D.; Stroh, C.; Juraeva, D.; Wang, D.; Johne, A.; Paik, P. K.
Abstract Title: ctDNA dynamics, prognostic markers, and mechanisms of resistance in tepotinib-treated MET exon 14 (METex14) skipping NSCLC in the VISION trial
Meeting Title: 14th Annual Navigation & Survivorship Conference of the Academy of Oncology Nurse And Patient Navigators (AONN+)
Abstract: Background: Oncology nurse navigators are integral members of multidisciplinary teams that manage patients with non--small cell lung cancer (NSCLC), including the 3%-4% of patients with mesenchymal-epithelial transition exon 14 (METex14) skipping mutation. This oncogenic driver confers a poor prognosis but sensitizes tumors to MET inhibitors. Tepotinib, an oral, selective MET inhibitor, showed robust, durable efficacy in METex14 NSCLC in the VISION trial. Objective: To support nurse navigators and other professionals managing these patients, we conducted an exploratory analysis of VISION to evaluate circulating tumor DNA (ctDNA) and MET-related biomarkers in liquid biopsy (LBx [ie, blood]) samples and their associations with clinical outcomes. Methods: Baseline, on-treatment and/or end-of-treatment (EOT) LBx from VISION were analyzed by ctDNA next-generation sequencing (NGS; Guardant360®) and enzyme-linked immunoassay for shed MET (sMET; a soluble form of the MET extracellular domain) and hepatocyte growth factor (HGF; the ligand for MET). Patients with baseline LBx NGS profiles (n=165) were classified as positive (L+) or negative (L-) for METex14 (all L- patients had METex14 by tissue NGS). On-treatment response was analyzed in L+ patients with 2 consecutive on-treatment samples (n=81). Confirmed molecular response (cMR) was defined as >75% depletion from baseline in METex14 variant allele frequency (VAF) in 2 consecutive on-treatment samples; molecular progression (MP) was defined as VAF increase from baseline in ≥1 on-treatment sample. Objective response rate (ORR), median duration of response (mDOR), median progression-free survival (mPFS), and median overall survival (mOS) were evaluated according to biomarker status. Mechanisms of acquired resistance were investigated in postprogression EOT samples. Data cut-off date was November 20, 2022. Results: Patients with high (>upper quartile, n=58) versus low (≤upper quartile, n=175) baseline HGF had numerically shorter mDOR and mPFS. Patients with low (≤lower quartile, n=61) versus high (>lower quartile, n=183) relative change in sMET from baseline had numerically higher ORR, mPFS, and mOS. In L- (n=51) versus L+ (n=114) patients, ORR was comparable, but mDOR and mPFS were longer. Seven of 10 patients with MET amplification, 1 of 5 patients with KRAS/NRAS mutation, 1 of 5 patients with PI3K/AKT pathway alterations, and 0 of 2 patients with EGFR mutations at baseline had objective response. Patients with tumor protein 53 (TP53) mutations (73/165) versus wild-type had comparable ORR but shorter mPFS (8.2 vs 11.3 mo, respectively). Patients with cMR (n=65 [80%]) versus MP (n=12 [15%]) had better outcomes (ORR: 63.1% vs 16.7%, respectively; mDOR: 18.5 vs 6.2 mo, respectively; mPFS: 11.2 vs 4.2 mo, respectively). At EOT, 9 of 73 patients (12%) had acquired MET kinase domain mutations and 9 of 73 (12%) had emerging alterations in KRAS, EGFR, MYC, BRAF, RB1, and ERBB2. Conclusions: In the largest on-treatment LBx biomarker dataset for an MET inhibitor in METex14 NSCLC, MR was associated with improved outcomes and TP53 mutation had negative prognostic significance. On-target secondary MET mutations and off-target bypass pathway activation were potential resistance mechanisms. These data can help to inform nurse navigators and other healthcare professionals managing patients receiving tepotinib for METex14 skipping NSCLC.
Keywords: carcinoma, non-small-cell lung; tumor markers, biological; dna; texas; outcomes (health care); oncology nurses; liquid biopsy; congresses and conferences -- texas; cell-free nucleic acids -- analysis
Journal Title: Journal of Oncology Navigation & Survivorship
Volume: 14
Issue: 11
Meeting Dates: 2022 Nov 15-19
Meeting Location: San Antonio, TX
ISSN: 2166-0999
Publisher: Green Hill HealthCare Communications, LLC  
Date Published: 2023-11-01
Start Page: 352
End Page: 353
Language: English
PROVIDER: EBSCOhost
PROVIDER: cinahl
DOI/URL:

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Notes: Meeting abstract: A3 -- Source: Cinahl