308P - The genomic landscape of non-small cell lung cancer (NSCLC) in East Asia using circulating tumour DNA (ctDNA) in clinical practice

Background

We investigated the landscape of clinically relevant mutations in ctDNA from NSCLC patients in East Asia tested by a commercially available comprehensive next generation sequencing (NGS) assay (Guardant360) as part of clinical practice. This assay identifies single nucleotide variants (SNV), insertions (ins) and deletions (del), fusions, and amplifications (amp), with complete exon sequencing of multiple genes including EGFR, ERBB2, and KRAS.

Methods

Test results from Hong Kong, Korea, Taiwan, Japan and Southeast Asia were reviewed (cut-off June 2020). We identified cases with a diagnosis of “lung cancer,” excluding neuroendocrine, sarcomatoid, and pure squamous histology. Samples from patients enrolled in prospective clinical trials were excluded. Clinically relevant biomarkers were mutations in EGFR, ERBB2, or KRAS; BRAF V600E; MET amp or exon 14 skipping; and ALK, ROS1, RET, or NTRK1 fusions. Synonymous mutations and variants of unknown significance were not considered.

Results

Plasma from 1219 advanced non-squamous NSCLC patients was tested. Samples came from 663 women and 556 men, median age 62 years. Median turnaround time was 7 days from sample receipt to report. ctDNA was identified in 1034 samples (85% detection rate), with median variant allele fraction 0.6%. There were 718 samples (69%) with alterations in at least one clinically relevant biomarker: EGFR (49%), KRAS (8%), ERBB2 (4%), ALK (3%), RET (2%), MET (2%), BRAF (1%), and ROS1 (<1%). Co-mutations were detected in <1%. Potentially actionable EGFR alterations other than L858R or exon 19 del were found in 106 samples (13%), including exon 19 ins (1); exon 20 ins (25); and activating SNV (80) such as L718X (14), L861Q (7), G719A (7), and E709A (5). KRAS G12C was present in 22 samples (2%).

Conclusions

In the clinical practice setting, comprehensive NGS detected relevant biomarkers in 69% of plasma samples with ctDNA from patients with advanced non-squamous NSCLC. Using a single assay, both common and rare driver mutations could be found in a timely manner, obviating the need for multiple tests to identify less common actionable alterations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Guardant Health AMEA.

Funding

Has not received any funding.

Disclosure

B.C. Cho: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MOGAM Institute; Honoraria (self), Research grant/Funding (institution): Dong-A ST; Honoraria (self), Research grant/Funding (institution), Licensing/Royalties: Champions Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Yuhan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Medpacto; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Pfizer; Honoraria (self): Guardant Health AMEA; Advisory/Consultancy: Takeda; Research grant/Funding (institution): AbbVie. H.H.F. Loong: Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer-Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli-Lilly; Advisory/Consultancy: Illumina; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Guardant Health; Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Mundipharma. H.R. Kim: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Roche. M. Lee: Full/Part-time employment: Guardant Health AMEA. S. Olsen: Full/Part-time employment: Guardant Health AMEA; Shareholder/Stockholder/Stock options: Guardant Health, Inc.; Shareholder/Stockholder/Stock options: AstraZeneca. All other authors have declared no conflicts of interest.