Genomic profiling of early-stage resectable non-small-cell lung cancer in a Malaysian private healthcare setting: Real-world clinical implications

Introduction: The prevalence of oncogenic driver mutations in early-stage resectable non-small-cell lung cancer (rNSCLC) in Malaysia remains unknown. This information may guide treatment decisions, especially tyrosine kinase inhibitor (TKI) use. We characterised the genomic landscape of early-stage NSCLC in a surgical cohort and explored its impact on TKI administration, particularly osimertinib. Materials and Methods: 146 patients who underwent curative resection for early-stage rNSCLC were included in this study. Real-time polymerase chain reaction (PCR) and next-generation sequencing (NGS) were used to identify genetic alterations in tumour samples. Associations between EGFR status and clinico-pathological characteristics were analysed using uni-and multivariate logistic regression. Results: A majority of patients were female non-smokers of Chinese ethnicity with an incidental adenocarcinoma. EGFR mutations were detected in 62.3% (n=91) of patients, with 93.4% harbouring single-locus mutations, primarily in exons 19 and 21. Co-mutations occurred in 11% (n=10) of EGFR-mutant cases, most frequently involving TP53, and less commonly CTNNB1, HER2/ErbB2, and PTEN. Six (6.6%) patients had multi-loci EGFR mutations. Female sex and higher tumour histological grade were independent predictors for EGFR mutations, while former/never smokers showed higher odds on univariate analysis. Among patients tested for PD-L1 (78.8%), 46.6% had negative expression (tumour proportion score <1%), with no correlation to EGFR status. Conclusion: This is the first genomic molecular profiling study to report exclusively on early-stage NSCLC in Malaysia. The high prevalence of EGFR mutations observed, predominantly involved sensitizing mutations at exons 19 and 21, and was associated with the female sex, a non- smoking status, higher tumour grade, but not PD-L1 expression. Early reflex genomic testing is vital to guide biomarker-driven peri-operative treatment strategies for rNSCLC.