1549P - A prospective study of circulating tumor DNA (ctDNA) genomic profiling in gastric or gastroesophageal junction (GEJ) cancer patients with recurrence after adjuvant chemotherapy: Liquid-GEAR trial

Background

The genomic profile of gastric or GEJ cancer is unclear in cases that have recurred after primary adjuvant chemotherapy. We investigated genomic alterations (GA) detected in ctDNA using a liquid biopsy test and compared the results to the those of the primary tumor.

Methods

This prospective observational study was conducted at 17 institutes from Jan 2021 to Dec 2022. Eligible patients (pts) had previously resected stage II or III gastric/GEJ cancer with recurrence after or during adjuvant chemotherapy. Whole blood was collected before chemotherapy for recurrent disease; ctDNA was analyzed using a next-generation sequencing gene panel (Guardant360). The primary endpoint was the detection rate of actionable GA with at least level 3 evidence by OncoKB for any cancer type. Secondary endpoints included a comparison of ctDNA and primary tumor GA profiles, and biomarkers relevant to clinical outcomes. A binomial test was used to determine with 90% probability that actionable GA were found in ctDNA in more than 5% of cases.

Results

Among 51 enrolled pts, 50 were available for analysis, 14% stage II and 86% stage III. The most common primary site was gastric body (56%) followed by gastric antrum (26%), and GEJ (12%). The number of metastatic sites was 1 for 76%, 2 for 18%, and 3 for 6% pts. Liquid biopsy analysis detected actionable GA in 64% [90%CI: 49.2-77.1] and actionable GA for targeted therapy in 36% pts [90%CI: 22.9-50.8, P=0.0075]:PIK3CA in 20%, ARID1A in 10%, ERBB2 in 8% (6% amplification and 2% mutation), ATM in 6%, and BRCA2, EGFR, IDH2, RAF1, and ROS1 in 2% pts each. MSI-high was detected in one patient. Comparison of primary tumor DNA and ctDNA at recurrence is ongoing.

Conclusions

Using ctDNA analysis, our study demonstrated that potentially actionable GA occur in nearly one-third of pts with recurrence after curative-intent treatment of stage II-III gastric/GEJ cancer. Genomic profiling should be strongly considered in this setting. We will compare these data with genomic analysis of primary tumor tissues.

Clinical trial identification

UMIN000043080.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Intramural Research Grants of St. Marianna University School of Medicine.

Disclosure

H. Takeda: Financial Interests, Personal, Invited Speaker: Taiho, MSD, BMS, Chugai. S. Suzuki: Financial Interests, Personal, Funding: Pfizer Japan Inc. Y. Kito: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo. A. Makiyama: Financial Interests, Personal, Invited Speaker: Eli Lilly, Taiho, Ono, Daiichi Sankyo, Bristol Myers Squibb. M. Nakamura: Financial Interests, Personal, Invited Speaker: Bayer Yakuhin, Ltd., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan Co., Ltd., Merck Bio Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., Merck & Co., Inc., Servier. Y. Sunakawa: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Bristol Myers Squibb, Chugai Pharmaceutical, Takeda, Taiho Pharmaceutical, Merck, Daiichi Sankyo, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda, Otsuka Pharma, Parexel International Inc., IQVIA, Ono Pharmaceutical, CMIC Shift Zero K.K., PRA Health Sciences, Inc., Amgen; Non-Financial Interests, Project Lead: Japan Clinical Cancer Research Organization. All other authors have declared no conflicts of interest.