Clinical benefit and cost of plasma-first next-generation sequencing in patients with newly diagnosed advanced non-small cell lung cancer in Ireland: The PLAN study

Abstract

Background: We report a pilot clinical trial investigating the feasibility of liquid biopsy genotyping (LBG) at the time of radiological suspicion of advanced NSCLC, incorporating a micro-cost model (MCM). (PLAsma Genomic Testing in Advanced NSCLC; The PLAN trial, ClinicalTrials.gov Identifier: NCT05542485).

Methods: Patients with a radiologic suspicion of stage III-IV lung cancer were recruited from four cancer centres in Ireland between August 2023 and July 2024. LBG was performed using the Archer LiquidplexTM NGS assay. The MCM considered staff time, consumables and capital costs and savings from avoidance of repeat tissue biopsy genotyping (TBG) or inappropriate systemic therapy such as immunotherapy for EGFR + NSCLC.

Results: A total of 138 patients were enrolled in the study with 38 excluded from the primary analysis (Squamous=16; SCLC = 22). Of patients that were eligible, LBG was completed in 100 % (100/100). TBG was completed in 68 % (68/100; insufficient tissue 20 %; 20/100; declining ECOG PS 12 %; 12/100). Repeat tissue biopsies were avoided in 12 % (12/100) of patients due to available LBG reports. The median calendar days from LBG to receipt of genomic report was 21 days shorter for LBG (z = -6.8, p < 0.01) versus TBG, as a median (range: 1-104 days). For evaluable paired cases with both TBG and LBG available (n = 68), concordance was 90 % (61/68). LBG resulted in detection of 5 actionable variants. LBG (€1135) was less than half the cost of TBG (€2404). LBG also resulted in overall cost savings of €20,288 (reduced TBG; use of immunotherapy).

Conclusions: LBG reduces the time to genomic diagnosis in patients with newly diagnosed NSCLC compared to tissue genotyping, identifies actionable variants not reported in tissue, and results in overall cost savings.

Keywords: Liquid biopsy; Lung cancer; Thoracic oncology.