Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial

• Published in: Nature medicine Vol. 30; no. 7; pp. 1923 - 1932
• Main Authors: Peters, Solange, Gadgeel, Shirish M., Mok, Tony, Nadal, Ernest, Kilickap, Saadettin, Swalduz, Aurélie, Cadranel, Jacques, Sugawara, Shunichi, Chiu, Chao-Hua, Yu, Chong-Jen, Moskovitz, Mor, Tanaka, Tomohiro, Nersesian, Rhea, Shagan, Sarah M., Maclennan, Margaret, Mathisen, Michael, Bhagawati-Prasad, Vijay, Diarra, Cheick, Assaf, Zoe June, Archer, Venice, Dziadziuszko, Rafal
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 19.06.2024; Nature Publishing Group
• Subjects: 692/53; 692/699/67; Biomarkers; Biomedical and Life Sciences; Biomedicine; Biopsy; Cancer Research; Decision making; Effectiveness; Health services; Infectious Diseases; Lung cancer; Metabolic Diseases; Metastases; Metastasis; Molecular Medicine; Neurosciences; Non-small cell lung carcinoma; Patients; Small cell lung carcinoma; Tissues
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-024-03008-4

Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D ( ROS1 -positive). Patients ≥18 years of age with stage IIIB/IV, ROS1 -positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1 -positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 . Results from this single-arm cohort of the BFAST trial showed that the clinical efficacy of entrectinib in patients with ROS1 -positive NSCLC, selected using liquid biopsies, is consistent with that seen in previous reports where patients were selected using tissue-based testing methods.