Abstract 692P
Background
Mutations (mt) in Epidermal Growth Factor Receptor (EGFR) are among the key actionable oncogenic drivers in LUAD, with exon 19 deletions and L858R mutation being the most common. Although they usually occur independently, some studies have observed a subset of patients (pts) with multiple actionable mts. However, frequency of these concurrent alterations (alts), with common driver EGFRm, as detected by ctDNA NGS in LUAD cases from AME, remains unexplored.
Methods
We reviewed results of Guardant360® ordered for patients (pts) with LUAD from AME as part of routine clinical practice through Jan 2024. Plasma samples underwent NGS analysis at a central laboratory. The prescribing physicians did not provide details regarding the testing sequence or prior treatment history. These findings were compared with data from two publicly available similar sources, MSK-M and AACR-Genie (ACR) v15.1.
Results
Analysis of 6988 samples from 5728 pts revealed median age of 61 years. Median mt count was 3 (range 1-93), with allelic frequency at 0.8% (range 0.02-73.6%). EGFRmt prevalence was 48%, 25%, and 26% in AME, MSK-M, and ACR databases. Distribution of EGFR variants was consistent across databases, except for T790M and C797S, which were more common in ctDNA cohorts. Cumulative frequencies of level 1-2 OncoKb alts co-occurring with driver EGFR mt were 28%, 18%, and 20% in AME, MSK-M, and ACR datasets. In the AME database, EGFR mt, including G719X, L861Q, S768I, and T790M, were the most frequent co-alts (15%), followed by MET amp (5%), ERBB2mt (3%), and MET mt (2%). Other noteworthy co-alts (ERBB2 amp, FGFR2/3, BRAF, and EGFR fusions) were observed at a 3% combined rate. In MSK-M and ACR, prevalence of most co-occuring OncoKb alts was similar to those in AME, except for EGFR mt (G719X, L861Q, S768I, and T790M), which were observed at 7% and 8%, respectively. Other noteworthy co-alts were observed at a 3% rate in both these datasets as well.
Conclusions
Comprehensive ctDNA NGS can identify driver EGFR mts and other informative co-alts for patients with LUAD. Frequency and types of such co-alts are mostly similar in AME and other regions.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Guardant Health AMEA, Singapore, 138567.
Funding
Guardant Health AMEA, Singapore, 138567.
Disclosure
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. 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. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck, Boronoi. N. Peled: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Eli Lilly, Bayer, Boehringer Ingelheim, MSD, Pfizer, Novartis, Novocure, Takeda, Rhenium, Guardant Health, Foundation Medicine; Financial Interests, Personal, Invited Speaker: Foundation Medicine, Guardant Health. S.M. Lim: Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Roche, GSK, Jiansu Hengrui, Amgen, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: BridgeBio Therapeutics, Oscotec. N. Sandhir, S. Olsen: Financial Interests, Personal, Full or part-time Employment: Guardant Health-AMEA. All other authors have declared no conflicts of interest.