310P - Genomic biomarker detection in East Asian clinical practice using circulating tumour DNA (ctDNA) from patients with gastrointestinal (GI) tract cancers

Background

Detection of genomic biomarkers in ctDNA may guide treatment decisions for patients with advanced stage GI tract cancers. We summarized the frequency of common and clinically relevant alterations from East Asian patients with common GI cancers whose blood was tested by a commercially available comprehensive next generation sequencing (NGS) assay (Guardant360).

Methods

Anonymized test results from Japan, Korea, Taiwan, Hong Kong, and Southeast Asia were reviewed (cut-off June 2020). We identified cases with a diagnosis of colorectal adenocarcinoma (CRC), pancreatic adenocarcinoma (PC), gastric and gastroesophageal adenocarcinoma (GEC), and biliary tract carcinoma (BTC). Samples from patients enrolled in prospective clinical trials were not included. Synonymous mutations and variants of unknown significance were excluded.

Results

Among 191 plasma samples from CRC patients, ctDNA was detected in 174 (91%). Alterations included TP53 (79%), APC (61%), KRAS (47%), PIK3CA (18%), FGFR1 amp (11%), NRAS (6%), BRAF V600E (6%), ERBB2 amp (5%), MET amp (5%), FGFR2 amp (4%). In 236 samples from PC patients (204 with ctDNA, 86%), alterations included: TP53 (70%), KRAS (69%), PIK3CA (4%), BRCA2 (3%), FGFR1 amp (3%), BRCA1 (1%). In 74 samples from GEC cases (63 with ctDNA, 85%), alterations included: TP53 (59%), ERBB2 amp (16%), KRAS (11%), PIK3CA (6%), FGFR2 amp (6%), MET amp (5%), FGFR1 amp (3%). In 97 samples from BTC patients (84 with ctDNA, 87%), alterations included: TP53 (60%), KRAS (17%), PIK3CA (13%), IDH1 (10%), ERBB2 (4%), FGFR1 amp (4%), IDH2 (1%), BRCA2 (1%), FGFR2 amp or fusion (1% each).

Conclusions

NGS of ctDNA from clinical samples identified common and clinically relevant genomic alterations in East Asian patients with advanced GI cancers. The type and frequency of alterations for each tumor type were similar to those previously reported from tumor tissue banks, although there may be enrichment for resistance mutations due to prior treatment. Given the ease of blood collection over repeat tissue biopsy, these data support consideration of ctDNA NGS for guiding treatment decisions in patients with advanced GI cancers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Guardant Health AMEA, Inc.

Funding

Guardant Health AMEA, Inc.

Disclosure

M. Muto: Research grant/Funding (institution): Chugai Pharma; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Mitsui Knowledge Industry; Research grant/Funding (institution): Sysmex; Research grant/Funding (institution): Riken Genesis; Research grant/Funding (institution): KBBM Kyoto Bridge for Breakthrough Medicine. M. Lee: Full/Part-time employment: Guardant Health AMEA, Inc. S. Olsen: Shareholder/Stockholder/Stock options: AstraZeneca; Shareholder/Stockholder/Stock options: Guardant Health, Inc.; Full/Part-time employment: Guardant Health AMEA, Inc. All other authors have declared no conflicts of interest.