Prevalence and treatment of human epidermal growth factor receptor 2-altered non-small cell lung cancer: a retrospective analysis and systematic literature review.

Human epidermal growth factor receptor 2 (HER2) is known for its oncogenic activities in diverse cancers, including non-small cell lung cancer (NSCLC). However, the prevalence of alterations in Malaysian NSCLC patients remains unreported. This study examined the prevalence and characteristics of mutations and amplification in a Malaysian cohort. Additionally, a systematic review was conducted to evaluate the global prevalence of alterations in NSCLC, as well as the efficacy of HER2-targeted therapies observed in clinical trials. NSCLC tumour samples received from October 2019 to December 2022 for next-generation sequencing diagnostics were included in the retrospective analysis. In this patient cohort, alteration was present in 5.8% of patients; 3.9% had mutations, 1.5% had amplifications and 0.4% were both -mutated and amplified. exon 20 insertions were the most common variants, detected in 47/59 (79.7%) of -mutated patients. Among cases with exon 20 insertions, the Y772_A775dup variant was found in 34 patient samples. -mutated patients were significantly younger than non--mutants (61 versus 64 years old; = 0.046) and were inclined to be female and never-smokers, albeit not statistically significant. Patients with amplification were more likely to have progressed post-tyrosine kinase inhibitor therapy ( = 0.015). The systematic review highlighted a global variation in the prevalence of alterations in NSCLC, ranging from 0.3% to 9.1% for mutations and 0.2% to 19% for amplification. Finally, phase II clinical trials involving altered NSCLC patients demonstrated promising treatment outcomes with trastuzumab deruxtecan, trastuzumab emtansine, pyrotinib, pyrotinib + apatinib and trastuzumab + pertuzumab + docetaxel. In conclusion, the prevalence of alteration among Malaysian NSCLC patients falls within the global range. A systematic review of clinical trials revealed promising treatment outcomes and Malaysian NSCLC patients with alterations are anticipated to similarly benefit from -targeted therapies.