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
122P - Distinct transcriptomic immune profiling and clinicopathological features of cribriform morphology in colorectal adenocarcinomas
Presenter: Abdelhakim Khellaf
Session: Poster Display
Resources:
Abstract
123P - Spatial molecular profiling identifies FGF20 upregulation on cancer-associated fibroblast and FGFR2-PI3K/Akt activation in tumor cells of sporadic early-onset colon cancer
Presenter: Dave Hoon
Session: Poster Display
Resources:
Abstract
124P - Characteristics, prognosis and therapeutic effects of non-V600 BRAF mutated colorectal cancer
Presenter: Lalida Arsa
Session: Poster Display
Resources:
Abstract
125P - Final results of APOLLON-11 and SOYUZ-APOLLON study: Multicentre prospective observational post-authorization study of bevacizumab biosimilar in patients with metastatic colorectal cancer in real-world practice
Presenter: Alexey Tryakin
Session: Poster Display
Resources:
Abstract
126P - From tumor height (TH) to tumor regression grade (TRG) in locally advanced rectal cancers (LARC) during total neadjuvant therapy (TNT): A retrospective analysis
Presenter: Valeria Pusceddu
Session: Poster Display
Resources:
Abstract
127P - A meta-analysis of efficacy and safety from head-to-head first-line (1L) trials of epidermal growth factor receptor inhibitors (EGFRIs) versus bevacizumab in combination with chemotherapy (CT) doublets in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) by sidedness
Presenter: Takayuki Yoshino
Session: Poster Display
Resources:
Abstract
128TiP - A phase II study of cadonilimab + FOLFOXIRI and bevacizumab as initial therapy for unresectable proficient mismatch repair/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC)
Presenter: Rongbo Lin
Session: Poster Display
Resources:
Abstract
140P - Prevalence of claudin-18 isoform 2 (CLDN18.2) positivity in locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mg/GEJ) adenocarcinoma in patients (pts) in the Asia region: Phase III SPOTLIGHT and GLOW studies
Presenter: Hoo Hwoei Fen Soo
Session: Poster Display
Resources:
Abstract
141P - Early phase trials outcomes in refractory upper GI cancers: A 10-year analysis from the SCRI UK phase I unit
Presenter: Antonella Cammarota
Session: Poster Display
Resources:
Abstract
142P - The survival impact of the addition of durvalumab to cisplatin/gemcitabine in advanced biliary tract cancer: A real-world, retrospective, multicentric study
Presenter: Silvia Foti
Session: Poster Display
Resources:
Abstract