Abstract 494P
Background
METa are oncogenic drivers or resistance mechanisms in many cancer types and are targets for anti-MET therapies. NGS of either tumor tissue or ctDNA can identify METa. The prevalence of METa and associated co-alterations using ctDNA NGS in AC from AME is unknown.
Methods
We reviewed the results of Guardant360 (Guardant Health, Inc; v2.9-2.12) ordered for patients with AC from AME as part of routine clinical practice through May 2024. This comprehensive genomic profiling assay identifies single-nucleotide variants (mts), insertions, deletions, and amplifications (amp); all exons are evaluated for MET. MET fusions were reported only in v2.12.
Results
Among 13,023 samples analyzed, median age was 62, with 52.6% female. Median variant allele frequency was 1.4% (range: 0.03-94.3%). Prevalence of METa in the entire cohort was 5.9%, among which amp was (3.1%), Exon 14 skipping mts (ex14sm; 1.4%), tyrosine kinase domain mts (TKDm; 0.9%), fusions (0.3%), and other oncogenic mts (OTm; 0.1%). METa was highest in lung cancers (LC; 7.3%), genitourinary cancers (4.8%), and gastrointestinal cancers (GIC; 3.6%). In LC, MET amp was highest (3.7%), followed by ex14sm (2.3%) and TKDm (1.3%). GIC showed amp (2.9%), ex14sm (0.03%), and TKDm (0.5%) as most common. Breast cancer had MET amp (1.2%), ex14sm (0.7%), and TKDm (0.3%). Prevalent Oncogenic/Likely oncogenic TKDm were D1228E/G/H/N (44.9%), Y1230C/D/H/S (25.8%), and H1094R/Y (7.9%). Most frequent co-alterations with MET mts included TP53 (60.2%), EGFR (24.2%), and PIK3CA (13.8%) mts; amps in EGFR (15.0%), PIK3CA (7.7%), and MET (6.0%); and fusions involving EML4-ALK (1.2%), FGFR3-TACC3 (0.7%), and KIF5B-RET (0.5%). Most common co-mutations with MET amps were TP53 (75.6%), EGFR (30.6%), and MET (12.5%). Common co-amps included EGFR (47.4%), CDK6 (17.9%), and BRAF (17.1%). Co-fusions involved EML4-ALK (1.9%), STRN-ALK (1.2%), and CCDC6-RET (0.7%).
Conclusions
Comprehensive ctDNA NGS can identify METa and associated co-alterations that may inform therapeutic decisions for patients with AC in AME.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Guardant Health-AMEA, Singapore, 138567.
Funding
Guardant Health-AMEA, Singapore, 138567.
Disclosure
B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen; Financial Interests, Personal, Member of Board of Directors: J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties, PDX, PDO, PDC Licensing Contract – not patent: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, JINTSbio, Hanmi, Vertical Bio AG, National Research Foundation of Korea, KHIDI, Therapex; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. N. Peled: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Eli Lilly, Bayer, Boehringer Ingelheim, Bristol Myers Squibb , Pfizer, Novartis, Novocure, Takeda, Rhenium, Guardant Health, Foundation Medicine; Financial Interests, Personal, Invited Speaker: Foundation Medicine, Guardant Health. S. Dawood: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Merck, Gilead; Financial Interests, Personal, Invited Speaker: Roche, MSD, BMS, Pfizer, Lilly, AstraZeneca, Caris; Financial Interests, Institutional, Research Grant: MSD, Amgen; Non-Financial Interests, Personal, Member: ASCO, ESMO. S. Khandelwal, N. Sandhir, S. Olsen: Financial Interests, Personal, Full or part-time Employment: Guardant Health-AMEA. All other authors have declared no conflicts of interest.