587P - Exploring the prevalence and characteristics of human epidermal growth factor receptor 2 (HER2) alterations in non-small cell lung cancer: Analysis from a Malaysian cohort

Background

HER2 is known for its oncogenic activities in diverse cancers, including non-small cell lung cancer (NSCLC). Despite its significance, the prevalence of HER2 alterations in Malaysian NSCLC patients remains unreported. This study examined the prevalence and characteristics of HER2 mutations in a Malaysian cohort.

Methods

Next-generation sequencing (NGS) results of NSCLC samples received from October 2019 to December 2022, were assessed to determine the prevalence of HER2 mutations and amplification, along with the patient characteristics.

Results

Out of 1373 cases analyzed, 79 patients (5.8%) exhibited HER2 alterations, with HER2 mutations (n=54, 3.9%), HER2 amplification (20, 1.5%), and mutation with amplification (5, 0.4%) being identified. Patients with HER2 mutations were significantly younger than non-HER2-mutant counterparts (median age 61 vs. 64 years old; p=0.046) and displayed a tendency to be female and never-smokers (not statistically significant, NS). Patients with HER2 amplification tended to be male and ex- or current smokers (NS). Furthermore, HER2 amplification was associated with post-TKI progression (p=0.015). HER2 exon 20 insertions were the most common HER2 mutations, affecting 47/59 patients. Notably, HER2 Y772_A775dup was the most frequently detected variant (n=34). HER2 exon 20 insertions were mutually exclusive with ALK, BRAF, EGFR, RET, ROS1 and MET alterations. Two patients with HER2 Y772_A775dup harboured KRAS alterations, one with KRAS amplification and the other KRAS K117N. EGFR sensitizing mutations were observed in 4 patients with HER2 S310S/Y variants. Eleven patients with HER2 amplification had EGFR sensitizing mutation; of these, 5 were post-TKI progression cases. TP53 mutations were common co-mutations seen with HER2 mutation (n=14) and HER2 amplification (9).

Conclusions

This prevalence of HER2 mutations was 4.3% and HER2 amplification was 1.8% in this cohort of Malaysian patients with NSCLC. These findings suggest that the availability of HER2-targeted therapies may hold promise for managing these patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AstraZeneca.

Disclosure

P. Rajadurai: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZenaca, Novartis, MSD; Financial Interests, Personal, Invited Speaker: ThermoFisher; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche. All other authors have declared no conflicts of interest.