Abstract 486P
Background
Changes in genomic profiles from primary to recurrent gastric or gastroesophageal junction (GEJ) cancers are not well characterized. We previously reported the primary endpoint of our study, describing actionable genomic alterations (GAs) detected at relapse (Takeda et al, ESMO 2023). Here we present results from a key secondary endpoint, a comparison of primary and relapsed tumor genomic profiles from gastric or GEJ cancer patients who underwent curative-intent surgery.
Methods
This multicenter study enrolled stage II or III gastric/GEJ cancer patients with recurrence after surgery and adjuvant chemotherapy at 17 centers from January 2021 to December 2023. We collected primary tumor specimens at surgery and blood samples at recurrence to compare changes in genomic profiles for each patient. Comprehensive genomic profiling (CGP) was performed on tumor tissue using panel tests selected by investigators, and on circulating tumor DNA (ctDNA) by Guardant360. Actionable GAs were defined as OncoKB level 3 or higher for any cancer types.
Results
Of 51 enrolled patients, DNA results from both primary tissue and blood samples collected at recurrence were available for 18 patients. All tissue CGP tests were conducted by FoundationOne CDx. The primary site was gastric in 78% and GEJ in 22% patients. The peritoneum was the most common recurrence site, followed by lymph nodes and liver. In the primary tumor, actionable GAs were detected in 67% of patients; short variants (SVs) of PIK3CA (33%) and amplifications of ERBB2 (28%) and EGFR (17%). In ctDNA at recurrence, actionable GAs were detected in 56%; PIK3CA SVs (28%) and ERBB2 amplification (17%). Notably, 6 patients (33%) had new actionable GAs in ctDNA not found in the primary tumor, including ERBB2 amplification and SVs of ERBB2 and PIK3CA. Loss of actionable GAs occurred in 8 (44%) patients, which included PIK3CA SVs as well as amplifications of ERBB2 and EGFR.
Conclusions
Our study suggests that certain actionable GAs not present in primary tumors may emerge in recurrent gastric/GEJ cancer. Therefore, liquid biopsy test could be a clinically useful tool to identify therapeutic targets for recurrent cases.
Clinical trial identification
UMIN-CTR [ID: UMIN000043080].
Legal entity responsible for the study
The authors.
Funding
St. Marianna University.
Disclosure
H. Takeda: Financial Interests, Personal, Invited Speaker: Taiho, MSD, BMS, Chugai. S. Suzuki: Financial Interests, Personal, Research Grant: Pfizer. Inc, MSD. Y. Kito: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical. A. Makiyama: Financial Interests, Personal, Invited Speaker: Eli Lilly, Taiho, Ono, Daiichi Sankyo, Bristol Myers Squibb. Y. Sunakawa: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Bristol Myers Squibb, Chugai Pharmaceutical, Takeda, Taiho Pharmaceutical, Merck Biopharma, Daiichi Sankyo, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Merck Biopharma; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda, Otsuka Pharm, 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.