lunes, 23 de diciembre de 2019

Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: Incremental yield of actionabl... - PubMed - NCBI

2019 Nov 26;139:207-215. doi: 10.1016/j.lungcan.2019.11.022. [Epub ahead of print]

Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: Incremental yield of actionable alterations and cost-effectiveness analysis.

Tan AC1, Lai GGY1, Tan GS2, Poon SY1, Doble B3, Lim TH2, Aung ZW1, Takano A4, Tan WL1, Ang MK5, Tan BS6, Devanand A7, Too CW6, Gogna A6, Ong BH8, Koh TPT1, Kanesvaran R5, Ng QS1, Jain A5, Rajasekaran T5, Lim AST4, Lim WT5, Toh CK5, Tan EH5, Lim TKH4, Tan DSW9.

Author information

1: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
2: Division of Pathology, Singapore General Hospital, Singapore.
3: Duke-NUS Medical School, National University of Singapore, Singapore.
4: Division of Pathology, Singapore General Hospital, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore.
5: Division of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore.
6: Duke-NUS Medical School, National University of Singapore, Singapore; Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore.
7: Duke-NUS Medical School, National University of Singapore, Singapore; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore.
8: Duke-NUS Medical School, National University of Singapore, Singapore; Department of Cardiothoracic Surgery, National Heart Centre Singapore, Singapore.
9: Division of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore. Electronic address: daniel.tan.s.w@singhealth.com.sg.

Abstract

OBJECTIVES:

There is an expanding list of therapeutically relevant biomarkers for non-small cell lung cancer (NSCLC), and molecular profiling at diagnosis is paramount. Tissue attrition in scaling traditional single biomarker assays from small biopsies is an increasingly encountered problem. We sought to compare the performance of targeted next-generation sequencing (NGS) panels with traditional assays and correlate the mutational landscape with PD-L1 status in Singaporean patients.

MATERIALS AND METHODS:

We identified consecutive patients diagnosed between Jan 2016 to Sep 2017 with residual tissue after standard molecular testing. Tissue samples were tested using a targeted NGS panel for DNA alterations (29 selected genes including BRAF, EGFR, ERBB2 and TP53) and an RNA fusion panel (ALK, ROS1 and RET). PD-L1 immunohistochemistry was also performed. A cost-effectiveness analysis of NGS compared to standard molecular testing was conducted.

RESULTS:

A total of 174 samples were evaluated: PD-L1 (n = 169), NGS DNA panel (n = 173) and RNA fusion (n = 119) testing. Median age was 68 years, 53 % were male, 58 % were never smokers, 85 % were Chinese, 66 % had stage IV disease and 95 % had adenocarcinoma histology. In patients profiled with NGS on DNA, EGFR (56 %), KRAS (14 %), BRAF (2 %) and ERBB2 (1 %) mutations were found. RNA fusion testing revealed fusions in ALK (6 %), RET (3 %) and ROS1 (1 %). Cost-effectiveness analysis demonstrated that compared to sequential testing in EGFR negative patients, upfront NGS testing would result in an additional 1 % of patients with actionable alterations for targeted therapy being identified without significant increases in testing cost or turnaround time.

CONCLUSIONS:

This study demonstrates that even in an EGFR mutant predominant population, upfront NGS represents a feasible, cost-effective method of diagnostic molecular profiling compared with sequential testing strategies. Our results support the implementation of diagnostic NGS in non-squamous NSCLC in Asia to allow patients access to the most appropriate personalized therapy.