Abstract 587P
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.
Resources from the same session
549P - Drug-induced interstitial lung disease in patients with non-small cell lung cancer treated with immunotherapy for postoperative recurrence: Evaluation of CT findings and histopathological findings of the background lung
Presenter: shodai fujimoto
Session: Poster Display
Resources:
Abstract
551P - Real-world incidence and outcomes of immune-related adverse events in NSCLC patients
Presenter: Andrea Knox
Session: Poster Display
Resources:
Abstract
552P - TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in Asian patients (pts) with previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs)
Presenter: Yasushi Goto
Session: Poster Display
Resources:
Abstract
553P - Preceding plasma EGFR vs upfront tissue NGS for advanced NSCLC in the Chinese population: A single centre experience in Hong Kong
Presenter: Janet Du
Session: Poster Display
Resources:
Abstract
554P - Comparison of the analytical performance of endobronchial ultrasound-guided transbronchial needle aspiration and other sampling methods for the Oncomine Dx target test: An observational study
Presenter: Kazuhito Miyazaki
Session: Poster Display
Resources:
Abstract
555P - Quality of life in patients with stage IV non-small cell lung cancer and the influence of druggable mutations over time: A prospective, territory-wide study in Hong Kong
Presenter: Jason C S Ho
Session: Poster Display
Resources:
Abstract
556P - Results from the phase I study on efficacy and safety of iruplinalkib (WX-0593) for anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) patients who received prior second-generation ALK tyrosine kinase inhibitors (TKIs)
Presenter: xuezhi Hao
Session: Poster Display
Resources:
Abstract
557P - Longitudinal plasma proteomic profiling of EML4-ALK positive lung cancer receiving ALK-TKIs therapy
Presenter: Shasha Wang
Session: Poster Display
Resources:
Abstract
558P - Treatment duration and adherence of brigatinib as second-line treatment after crizotinib for ALK+ NSCLC in South Korea
Presenter: Jeong Eun Lee
Session: Poster Display
Resources:
Abstract
559P - Comprehensive survey of AACR GENIE database revealed a wide range of TMB distribution among all three classes (I, II, III) of BRAF mutated NSCLC
Presenter: Zhaohui Arter
Session: Poster Display
Resources:
Abstract