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

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.