Genomic Landscape of Non-Small Cell Lung Cancer (NSCLC) in East Asia Using Circulating Tumor DNA (ctDNA) in Clinical Practice |
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Authors: | Byoung Chul Cho Herbert H F Loong Chun-Ming Tsai Man Lung P Teo Hye Ryun Kim Sun Min Lim Suyog Jain Steve Olsen Keunchil Park |
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Institution: | 1.Division of Medical Oncology, Yonsei Cancer Center, Seoul 03722, Korea; (B.C.C.); (H.R.K.); (S.M.L.);2.Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, China;3.Department of Oncology, Veterans General Hospital, Taipei 112, Taiwan;4.ICON Cancer Centre, Hong Kong SAR, China;5.Department of Medical Affairs, Guardant Health AMEA, Singapore 138543, Singapore;6.Sungkyunkwan University School of Medicine, Seoul 2066, Korea; |
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Abstract: | Plasma-based next-generation sequencing (NGS) has demonstrated the potential to guide the personalized treatment of non-small cell lung cancer (NSCLC). Inherent differences in mutational genomic profiles of NSCLC exist between Asian and Western populations. However, the published mutational genomic data of NSCLC has largely focused on Western populations. We retrospectively analyzed results from comprehensive NGS of plasma (Guardant360®) from patients with advanced non-squamous NSCLC, as seen in clinical practice. Tests were ordered between January 2016 and December 2020 in Hong Kong, Korea, Taiwan, Japan and Southeast Asia. The assay identified single-nucleotide variants (SNV), insertions and deletions, and fusions and amplifications in 74 genes. In total, 1608 plasma samples from patients with advanced non-squamous NSCLC were tested. The median turnaround time for test results was 7 days. Of the samples with detectable ctDNA (85.6%), 68.3% had alterations in at least one NCCN-recommended NSCLC biomarker. EGFR driver mutations were most frequent (48.6%), followed by alterations of KRAS (7.9%), ERBB2 (4.1%) and ALK (2.5%). Co-mutations of EGFR and KRAS occurred in 4.7% of samples. KRAS G12C was identified in 18.6% of all samples with KRAS mutations. Common mutations, such as exon 19 deletions and L858R, accounted for 88.4% of EGFR driver mutations. Among the samples with any EGFR driver mutation, T790M was present in 36.9%, including 7.7% with additional alterations associated with osimertinib resistance (MET amplification, C797X). Comprehensive plasma-based NGS provided the timely and clinically informative mutational genomic profiling of advanced non-squamous NSCLC in East Asian patients. |
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Keywords: | genomic profiling next-generation sequencing liquid biopsy non-small cell lung cancer East Asia |
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