499P - Prevalence of uncommon epidermal growth factor receptor (EGFR) alterations detected by circulating tumour DNA (ctDNA) in non-small cell lung cancer (NSCLC) patients in Hong Kong

Background

EGFR mutations occur in about half of the advanced non-squamous NSCLC patients in East Asia. Majority of the common activating mutations like L858R, exon 19 deletions (del) and T790M are detected by hot spot test methods in Hong Kong. However, hot spot test may not detect other uncommon EGFR alterations like point mutations, exon 20 insertions and amplifications, in which the best treatment remains undefined. Using a comprehensive liquid biopsy we investigated the prevalence of these uncommon EGFR alterations in ctDNA from NSCLC patients.

Methods

All Guardant360 (Guardant Health, Redwood City, CA) requests ordered in Hong Kong between Jan 2016 and June 2019 were reviewed. This is a next-generation ctDNA sequencing (NGS) panel of 74 cancer-related genes, including complete exon sequencing of EGFR. We identified cases with a diagnosis of “lung cancer” and excluded pure squamous, small cell, neuroendocrine and sarcomatoid histology. Uncommon EGFR alterations, defined as amplification or mutations other than L858R, exon 19 del, or T790M were identified. Synonymous mutations and variants of unknown significance were excluded. Demographics and impact of results to subsequent management will be analyzed and presented later.

Results

A total of 282 non-squamous NSCLC patients were tested. Samples came from 146 women and 136 men, with a median age 60. ctDNA was identified in 241 samples (85.5% detection rate). EGFR alterations were identified in 95 samples (39.4%), including L858R (48), exon 19 del (27), and T790M (24). Uncommon alterations were found in 47 of 95 EGFR cases (49.5%); 18 of these had no co-existing common EGFR or other driver mutation. These included amplifications (8); exon 20 insertions (8); L861Q (2); and other point mutations (4); 4 cases had an uncommon mutation with amplification.

Conclusions

Using a comprehensive ctDNA NGS panel, 47 out of 241 (19.5%) non-squamous NSCLC patients with uncommon EGFR alterations were detected. Novel NGS methods can help identify this group of patients with unmet needs for a gene-directed therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Guardant Health AMEA.

Funding

Has not received any funding.

Disclosure

O.S.H. Chan: Full / Part-time employment: Hong Kong Integrated Oncology Centre; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Merck Sharp & Dohme. G.Y. Cheung: Full / Part-time employment: Sanomics Limited. M.M.L. 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.