Upfront liquid next-generation sequencing in treatment-naïve advanced non-small cell lung cancer patients: A prospective randomised study in the Taiwanese health system

Ching-Yao Yang; Jin-Yuan Shih; Wei-Yu Liao; Chao-Chi Ho; Chia-Lin Hsu; Tzu-Hsiu Tsai; Shang-Gin Wu; Yen-Ting Lin; Wei-Hsun Hsu; Suyog Jain; Steve Olsen; James Chih-Hsin Yang; Chong-Jen Yu; Pan-Chyr Yang

doi:10.1016/j.ejca.2023.113310

Upfront liquid next-generation sequencing in treatment-naïve advanced non-small cell lung cancer patients: A prospective randomised study in the Taiwanese health system

Eur J Cancer. 2023 Nov:193:113310. doi: 10.1016/j.ejca.2023.113310. Epub 2023 Aug 28.

Authors

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
² Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: jyshih@ntu.edu.tw.
³ Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan.
⁴ Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Deparment of Medical Affairs, Guardant Health AMEA, Singapore.
⁶ Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
⁷ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan.

PMID: 37722270
DOI: 10.1016/j.ejca.2023.113310

Abstract

Background: Next-generation sequencing (NGS) of plasma cell-free DNA identifies driver mutations in advanced non-small cell lung cancer (NSCLC) and may complement routine molecular evaluation. The utility of liquid NGS at the start of tumour workup is undetermined.

Methods: This is a randomised study of patients with suspected advanced NSCLC. All patients received blood liquid NGS testing at their first clinic visit and underwent standard histological diagnosis and tissue genotyping, encompassing polymerase chain reaction based methods for EGFR mutation, immunohistochemical (IHC) staining for ALK fusion and BRAF V600E mutation, and an IHC screening followed by confirmation using fluorescence in situ hybridization confirmation for ROS1 fusion. They were then randomly assigned to receive NGS results either after tissue genotyping (Group A) or as soon as possible after histological diagnosis of advanced NSCLC (Group B). The study measured time to start of systemic treatment as the primary endpoint and secondary endpoints included biomarker discovery rate, objective response rate (ORR), and progression-free survival (PFS).

Results: This study enroled 180 patients with suspected advanced NSCLC, randomised into two groups. 63 patients in Group A and 59 in Group B with advanced NSCLC were confirmed as advanced NSCLC and analysed. Most had adenocarcinoma (Group A: 77.8%, Group B: 79.7%). The prevalence of EGFR mutations in the two groups was similar (Group A: 57.1%; Group B: 56.6%). Other driver alterations were rare. The median time to treatment was shorter in Group B (20 days) than in Group A (28 days). ORR and PFS did not differ between groups significantly. Liquid NGS had high concordance with tissue testing and identified driver mutations in 42.6% (20/47) of tissue-negative cases.

Conclusion: Performing liquid NGS at the initial clinic visit for suspected advanced NSCLC identifies more patients suitable for targeted therapies and shortens time to the start of treatment.

Keywords: CfDNA; Liquid biopsy; Lung cancer; NGS.