482MO - Clinical usefulness of next-generation sequencing for metastatic or unresectable gastric cancer in molecular profiling-guided therapy era

Background

Next-generation sequencing (NGS) is actively used for molecular profiling-guided therapy (MGT) across types of solid tumors. However, the clinical roles of NGS remain unclear in metastatic or unresectable gastric cancer (mGC). Thus, we aimed to elucidate the clinical usefulness of NGS in mGC.

Methods

Targeted NGS was performed using 4 versions of the customized SNUH FiRST Cancer Panel with different numbers (145 to 336) of cancer-related genes. The oncogenic variants are classified into five levels of evidence (I to V) based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Druggable genes were defined as genes with potentially targeted agents and the oncogenic variants, including mutations (mut), amplifications (amp), and fusions (fus) in ERBB2, PIK3CA, ATM, BRCA1/2, BRAF, KRAS, FGFR2, MET, EGFR, MDM2, ROS1, RET, and NTRK. Overall survival was defined as the time from the start date of 1st line treatment to the death date.

Results

From December 2015 to December 2023, NGS was performed on 262 patients with mGC. A total of 232 (88.5%) had at least one oncogenic variant. Druggable genes were found in 94 (35.9%); PIK3CA mut (9.2%), ERBB2 amp (7.6%), ATM mut (5.0%), FGFR2 amp (4.2%), BRCA2 mut (3.4%), MDM2 amp (3.4%), MET amp (3.1%), ERBB2 mut (2.3%), EGFR amp (1.1%), BRCA1 mut (0.8%), BRAF mut (0.8%), high microsatellite instability (MSI) (3.4%) and high tumor mutational burden (TMB) (3.1%). Among 252 receiving systemic treatment, 20 (7.9%), including 12 enrolled in clinical trials, received MGT (Sub1), while 70 (27.8%) with druggable genes did not receive MGT (Sub2), and 162 (64.3%) without druggable genes received standard treatment (Sub3). A higher proportion of patients in Sub1 received 3rd or later lines of treatment compared with other Subs (Sub1, 70.0%; Sub2, 27.1%; Sub3, 37.0%; p=0.002). Median overall survival (mOS) was 24.0 months (95% CI 20.1-28.0) in Sub1, 22.6 months (95% CI 15.3-29.9) in Sub2, and 19.7 months (95% CI 17.7-21.7) in Sub3 (p=0.409).

Conclusions

NGS testing can identify considerable candidates for MGT and provide more treatment opportunities in patients with mGC. The development of agonistic clinical trials and flexible use of off-label drugs are necessary for MGT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.