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Clinical Trial
. 2025 Apr;20(4):437-450.
doi: 10.1016/j.jtho.2024.12.011. Epub 2024 Dec 16.

LIBELULE: A Randomized Phase III Study to Evaluate the Clinical Relevance of Early Liquid Biopsy in Patients With Suspicious Metastatic Lung Cancer

Aurélie Swalduz  1 , Camille Schiffler  2 , Hubert Curcio  3 , Bana Ambasager  4 , Gabriel Le Moel  5 , Didier Debieuvre  6 , Jean-Marc Dot  7 , Michael Duruisseaux  8 , Pierre Fournel  9 , Luc Odier  10 , Sylvie Demolombe  11 , Acya Bizieux-Thaminy  12 , Annie Peytier  13 , Roland Schott  14 , Stéphane Hominal  15 , Claire Tissot  16 , Pierre Bombaron  17 , Séverine Metzger  2 , Mathilde Donnat  2 , Sandra Ortiz-Cuaran  18 , Nitzan Rosenfeld  19 , Christodoulos Pipinikas  4 , Pierre Saintigny  20 , Maurice Pérol  21
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Free article
Clinical Trial

LIBELULE: A Randomized Phase III Study to Evaluate the Clinical Relevance of Early Liquid Biopsy in Patients With Suspicious Metastatic Lung Cancer

Aurélie Swalduz et al. J Thorac Oncol. 2025 Apr.
Free article

Abstract

Objectives: Genomic profiling is a major component for first-line treatment decisions in patients with NSCLC and the timeliness of biomarker testing is essential to improve time to treatment initiation (TTI) or avoid inappropriate treatment.

Methods: The phase III LIquid Biopsy for the Early detection of LUng cancer Lesion trial (NCT03721120) included patients with radiological suspicion of advanced lung cancer. They were randomized (1:1), the control arm receiving diagnostic procedures according to each center's practice, and the liquid biopsy arm with additional testing performed at the first visit using the InVisionFirst-Lung assay. Treatment initiation and type were defined according to the European Society for Medical Oncology guidelines. Primary endpoint was the time from randomization to initiation of appropriate treatment on the basis of informative genomic and pathological results in the intention-to-treat population.

Results: A total of 319 patients were enrolled (liquid biopsy [LB]: 161; control: 158). The median age was 68 years, 28.8% were non-smokers, 18.1% had a performance status of 2 or higher, and 56.7% had adenocarcinoma. In the LB arm, 81% of patients had circulating tumor DNA findings. The mean TTI was not significantly reduced (LB: 29.0 d; control 34 d (p = 0.26)). Sensitivity analyses found a shorter TTI in patients from the LB arm who received systemic treatment (LB: 29.1 d; control: 38.9 d, p = 0.01), in patients with advanced non-squamous NSCLC (LB: 29.5 d; control: 40.3 d, p = 0.01), and in patients with first-line targetable alterations (LB: 21d; control 37.4 d) (p = 0.004). Time to contributory genomic results was significantly reduced (LB: 17.9 d; control: 25.6 d, p < 0.001).

Conclusion: Early liquid biopsy testing did not significantly shorten the TTI in unselected patients referred for suspected advanced lung cancer. Nevertheless, it could reduce the TTI in patients eligible for systemic treatment, particularly for those with actionable alterations.

Keywords: Circulating tumor DNA (ctDNA); Liquid biopsy; Next-generation sequencing (NGS); Non–small cell lung cancer (NSCLC); Precision oncology; Treatment initiation.

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Conflict of interest statement

Disclosure Dr. Swalduz is a consultant for Amgen, AstraZeneca, Roche, Pfizer, Sanofi, Janssen, Pfizer, and Takeda; reports personal fees from AstraZeneca, Roche, Pfizer, MSD, Boehringer-Ingelheim, Daiichi Sankyo, Sanofi, Takeda, Janssen, and Amgen; has received support for meetings or travel from Roche, Janssen, Pfizer, and Takeda. Dr. Debieuvre has received research funding from Roche, AstraZeneca, Lilly, BMS, Boehringer-Ingelheim, Chiesi, Chugaï, Pfizer, MSD, Novartis, GSK, Sandoz, Takeda, OSE Immunotherapeutics, Bayer, Janssen, Sanofi, Aventis, Amgen; is a consultant for Roche, BMS, Pfizer, OSE Immunotherapeutics, Amgen; reports personal fees from AstraZeneca, Chugaï, Roche, Novartis, Pfizer, MSD, BMS, Boehringer-Ingelheim, Gilead, Amgen; has received support for meetings or travel from Roche, Boehringer-Ingelheim, Novartis, Pfizer, BMS, AstraZeneca, MSD, GSK; and declare Participation on a Data Safety Monitoring Board or Advisory Board for Roche, Boehringer-Ingelheim, Pfizer, MSD, BMS, Novartis, AstraZeneca, Amgen. Dr. Duruisseaux has received research funding from Pfizer, AstraZeneca, Takeda, Blueprint, Merus, and BMS; is a consultant for Roche, BMS, Pfizer, Amgen, Boehringer Ingelheim, abbvie, Takeda, MSD, Novartis, Gamamabs Pharma, GSK, Guardant, and AstraZeneca; reports personal fees from AstraZeneca, Roche, Novartis, Pfizer, MSD, BMS, Boehringer-Ingelheim, Amgen, Guardant, Janssen; has received support for meetings or travel from Roche. Dr. Fournel reports personal fees from Sanofi, MSD, AstraZeneca; has received support for meetings or travel from Takeda; and declares participation on the Data Safety Monitoring Board or Advisory Board for Sanofi, MSD Roland Schott is a consultant for Roche, BMS, and AstraZeneca; reports personal fees from Roche, BMS, and AstraZeneca; has received support for meetings or travel from Roche, Takeda, MSD, Pfizer, Ipsen. Dr. Tissot is a consultant for Amgen, AstraZeneca, BMS, MSD, and Sanofi; and reports personal fees from BMS, AstraZeneca, MSD, Boehringer-Ingelheim, Sanofi, and Amgen. Dr. Rosenfeld declares to receive royalties or licenses, consulting fees, support for meetings or travel, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid; Stock or stock options by Inivata Ltd., NeoGenomics Inc.; he declares to receive Patents planned, issued or pending from Inivata Ltd., NeoGenomics Inc and Cancer Research UK and University of Cambridge. Dr. Saintigny declares to have support by Inivata for funded ctDNA analysis of the LIBELULE trial. Dr. Pérol is a consultant for BMS, MSD, AstraZeneca, Roche, Daiichi Sankyo, Janssen, Ipsen, Esai, GSK, eli Lilly, Pfizer, Takeda, Novocure; reports personal fees from AstraZeneca, Pfizer, MSD, BMS, Janssen, AnHeart Therapeutics, Sanofi, and Takeda; has received payment for expert testimony from BMS, AstraZeneca, Roche, Janssen; has received support for meetings or travel from Roche, BMS, MSD, AstraZeneca, Pfizer, Takeda; and declare Participation on a Data Safety Monitoring Board or Advisory Board for Roche and Pharmamar. The remaining authors declare no conflict of interest.

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