Genomic profiling of early-stage resectable non-small-cell lung cancer in a Malaysian private healthcare setting: Real-world clinical implications.
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.
146 patients who underwent curative resection for early-stage rNSCLC were included in this study. Real-time polymerase chain reaction (PCR) and nextgeneration 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.
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 EGFRmutant 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.
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.
146 patients who underwent curative resection for early-stage rNSCLC were included in this study. Real-time polymerase chain reaction (PCR) and nextgeneration 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.
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 EGFRmutant 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.
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.
Authors
Sachithanandan Sachithanandan, Hoh Hoh, Lam Lam, Low Low, Yap Yap, Hassanudin Hassanudin, Ten Ten, Tan Tan, Naim Naim, Lutfi Lutfi, Yong Yong, Sachithananthan Sachithananthan, Yap Yap, Rajadurai Rajadurai
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