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
163P - Chemotherapy versus palliative radiotherapy in advanced inoperable gall bladder cancer
Presenter: Vimal Sekar
Session: Poster Display
Resources:
Abstract
164P - Neoadjuvant immune checkpoints inhibitors plus chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma
Presenter: Ming-Wei Kao
Session: Poster Display
Resources:
Abstract
165P - BMI impact on the prognosis of unresectable HCC patients receiving first-line lenvatinib or atezolizumab plus bevacizumab
Presenter: Elisabeth Amadeo
Session: Poster Display
Resources:
Abstract
166P - Preoperative risk factors strongly related to early recurrence after R0 resection of gallbladder cancer
Presenter: SANGHUN LEE
Session: Poster Display
Resources:
Abstract
167P - Peripheral blood neutrophil-to-lymphocyte ratio correlated with serum IL-8 level and predict the outcome of hepatocellular carcinoma patients treated with immune-targeted combination therapy
Presenter: Xuenan Peng
Session: Poster Display
Resources:
Abstract
168P - Real-world clinicopathological characteristics and treatment patterns of esophageal cancer patients in China
Presenter: Zhihao Lu
Session: Poster Display
Resources:
Abstract
169P - Conversion response and prognostic factors in HCC patients with macrovascular invasion treated with atezolizumab plus bevacizumab
Presenter: xiaodong Zhu
Session: Poster Display
Resources:
Abstract
170P - Atezolizumab plus bevacizumab (A+B) versus lenvatinib for BCLC-B stage of patients with hepatocellular carcinoma (HCC): A large real-life worldwide population
Presenter: Francesco Vitiello
Session: Poster Display
Resources:
Abstract
171P - Retrospective study of the correlation between proteinuria and renal function in patients (pts) with unresectable hepatocellular carcinoma (uHCC) treated with atezolizumab plus bevacizumab (Atezo+Bev): ARISE study
Presenter: Kazuomi Ueshima
Session: Poster Display
Resources:
Abstract
172P - Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2-positive locally advanced/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary efficacy and safety from the phase II single-arm DESTINY-Gastric06 (DG06) trial
Presenter: Zhi Peng
Session: Poster Display
Resources:
Abstract