Spectrum of rare EGFR mutations in Indonesian lung adenocarcinoma: Findings from an 8-year analysis of 4,778 cases highlighting the need for advanced targeted therapies

Lung cancer patients in Indonesia exhibit a high prevalence of epidermal growth factor receptor (<i>EGFR</i>) mutations, with a substantial proportion attributed to rare or uncommon variants. The clinical significance of rare <i>EGFR</i> mutations lies in their differential sensitivity to tyrosine kinase inhibitors (TKIs). While they are frequently resistant to first- and second-generation TKIs, they often respond to third-generation TKIs, necessitating tailored treatment options. The need for improving access to advanced targeted therapies in Indonesia also highlights the importance of conducting research on rare <i>EGFR</i> mutations. The aim of this study was to identify the spectrum and frequency of <i>EGFR</i> mutations in patients with lung adenocarcinoma in Indonesia. A cross-sectional observational study with total sampling was conducted from January 2016 to April 2024 to investigate <i>EGFR</i> mutation profiles in lung adenocarcinoma patients. Samples were acquired from patients with a confirmed anatomical pathology diagnosis from various healthcare centers across Indonesia. A total of 4,778 samples were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) on various specimen types to determine <i>EGFR</i> mutation prevalence and patterns. Associations between demographic data and <i>EGFR</i> mutation status were assessed. <i>EGFR</i> mutations were detected in 54.6% of samples, with common mutations (exon 19 deletions/insertions and point mutation L858R) comprising 76.2% of positive cases and rare mutations (exon 20 insertions, point mutation G719X, S768I, T790M, and L861Q) accounted for 20.3%. Significant associations were found between geographic origin, age, and sex with <i>EGFR</i> mutation status. This study confirms substantial genetic variability and geographical differences in <i>EGFR</i> mutations among Indonesian lung adenocarcinoma patients, emphasizing the urgent need for further research to prompt enhanced molecular diagnostics and targeted therapies in the region.