Blood-based next-generation sequencing (NGS) can identify ALK fusions and guide treatment in patients with advanced/metastatic non-small cell lung cancer (NSCLC), according to a study published in the Journal of Thoracic Oncology.

The study authors explained that standard approaches to biomarker testing in NSCLC utilize tissue biopsies, but obtaining sufficient tumor tissue can be challenging, and repeated biopsies may not be feasible.

The Blood-First Assay Screening Trial (BFAST; Identifier: NCT03178552) was designed to test treatment selection for patients with advanced/metastatic NSCLC based on findings from blood-based NGS rather than tissue biopsy.

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The ongoing phase 2/3 trial currently includes 6 cohorts in which investigators are testing the efficacy and safety of therapy directed at specific biomarkers. In the Journal of Thoracic Oncology, the investigators reported results from the ALK cohort.

The investigators screened 2219 patients for actionable mutations using the blood-based NGS assay, which yielded results in 98.6% of cases.

There were 119 patients with ALK-positive NSCLC, and 87 of them were eligible to receive treatment with the ALK inhibitor alectinib. The median treatment duration was 11.1 months, the median dose intensity was 99.9%, and the median follow-up was 12.6 months.

The objective response rate (ORR) was 92.0% by independent review and 87.4% by investigator assessment. According to investigators, the ORR was 84.6% in patients without central nervous system (CNS) disease at baseline and 91.4% in patients with CNS disease at baseline.

The median duration of response was not reached, and the 12-month duration of response was 75.9%, according to investigator assessment.

The median progression free-survival (PFS) was not reached. The investigator-assessed PFS rates were 90.7% at 6 months and 78.4% at 12 months.

Safety data were consistent with the known tolerability profile of alectinib, according to the investigators. Serious adverse events (AEs) were reported in 24% of patients, and these AEs were considered treatment-related in 6% of patients.

Grade 3-4 AEs occurred in 35% of patients, and the most common of these were dyspnea (n=6), anemia (n=4), and asthenia (n=3).

There was 1 unexplained death that was considered unrelated to treatment.

“First-line detection of ALK fusions using a validated blood-based NGS assay in BFAST predicts for high ORR and significant clinical benefit in patients with metastatic NSCLC receiving alectinib,” the investigators concluded. “These results demonstrate the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive disease.”

Disclosures: This research was supported by F. Hoffmann-La Roche Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Dziadziuszko R, Mok T, Peters S, et al. Blood First Assay Screening Trial (BFAST) in treatment-naïve advanced or metastatic non-small cell lung cancer: Initial results of the phase 2 ALK-positive cohort. J Thorac Oncol. Published online July 22, 2021. doi:10.1016/j.jtho.2021.07.008