ESMO Congress 2023 | OncologyPRO

Abstract 198P

Background

Recent advances have transformed care for HER2-positive gastrointestinal cancer. However, the clinical utility of NGS-based techniques for determining HER2 status in GI cancer has been limited. Here, we detail our experience regarding the assessment of HER2 alterations in GI cancer.

Methods

626 colorectal cancer (CRC) samples, 80 esophageal cancer (ESCA) samples, 153 esophagogastric junction cancer (EGJC) samples, and 286 gastric cancer (GC) samples were collected from August 2021 to April 2023. Among them, there were 82 CRC plasma samples, 33 GC plasma samples, 7 ESCA plasma samples, and 22 EGJC plasma samples. All specimens were detected by OncoDrug-Seq 603-gene panel assay through NGS using Illumina NovaSeq 6000. For plasmas, HER2 amplification defined as HER2 copy number >2.22 was identified. For tissues, HER2 amplification defined as HER2 copy number >6.00 was identified.

Results

For tissue samples, ERBB2 amplification was detected in 0.74% of CRCs, 3.56% of GCs, 1.37% of ESCAs, and 3.05% of EGJCs. Only 2 GC cases (6.06%) were found to have ERBB2 amplification for plasma samples. No ERBB2-amplified CRCs showed mismatch-repair deficiency. ERBB2 amplification is anti-correlated with RAS/RAF mutations in CRCs (p=0.047). Interestingly, ERBB2 amplification was associated with microsatellite stability in GCs (p=0.00078). Other driver alterations were not present in the ERBB2-amplified cases that currently have targeted therapies approved by the FDA including NTRK fusion, RET fusion, and BRAF V600E mutation.

Conclusions

The proportions of ERBB2 amplification in GCs and EGJCs were relatively high. The high positive rate in GC plasma samples is worthy of attention. The mutational landscape of ERBB2-amplified cases provides novel insights that can help guide further patient-personalized therapy.