Blood First Assay Screening Trial (BFAST) in Treatment-Naive Advanced or Metastatic NSCLC: Initial Results of the Phase 2 ALK-Positive Cohort

Rafal Dziadziuszko; Tony Mok; Solange Peters; Ji-Youn Han; Jorge Alatorre-Alexander; Natasha Leighl; Virote Sriuranpong; Maurice Pérol; Gilberto de Castro Junior; Ernest Nadal; Filippo de Marinis; Osvaldo Arén Frontera; Daniel S W Tan; Dae Ho Lee; Hye Ryun Kim; Mark Yan; Todd Riehl; Erica Schleifman; Sarah M Paul; Simonetta Mocci; Rajesh Patel; Zoe June Assaf; David S Shames; Michael S Mathisen; Shirish M Gadgeel

doi:10.1016/j.jtho.2021.07.008

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Blood First Assay Screening Trial (BFAST) in Treatment-Naive Advanced or Metastatic NSCLC: Initial Results of the Phase 2 ALK-Positive Cohort

Authors: Rafal Dziadziuszko ; Tony Mok ; Solange Peters ; Ji-Youn Han ; Jorge Alatorre-Alexander ; Natasha Leighl ; Virote Sriuranpong ; Maurice Pérol ; Gilberto de Castro Junior ; Ernest Nadal ; Filippo de Marinis ; Osvaldo Arén Frontera ; Daniel S W Tan ; Dae Ho Lee ; Hye Ryun Kim ; Mark Yan ; Todd Riehl ; Erica Schleifman ; Sarah M Paul ; Simonetta Mocci ; Rajesh Patel ; Zoe June Assaf ; David S Shames ; Michael S Mathisen ; Shirish M Gadgeel

Citation: JOURNAL OF THORACIC ONCOLOGY, Vol.16(12) : 2040-2050, 2021-12

Journal Title: JOURNAL OF THORACIC ONCOLOGY

ISSN: 1556-0864

Issue Date: 2021-12

MeSH: Anaplastic Lymphoma Kinase / genetics ; Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / genetics ; Cohort Studies ; Crizotinib ; Humans ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Protein Kinase Inhibitors / therapeutic use

Keywords: ALK-positive ; Alectinib ; Blood-based assay ; NSCLC ; Next-generation sequencing

Abstract: Introduction: The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort.

Methods: Patients aged more than or equal to 18 years with stage IIIB or IV NSCLC and ALK rearrangements detected by blood-based NGS using hybrid capture technology (FoundationACT) received alectinib 600 mg twice daily. Asymptomatic or treated central nervous system (CNS) metastases were permitted. Primary end point was investigator-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors version 1.1). Secondary end points were independent review facility-assessed ORR, duration of response, progression-free survival (PFS), overall survival, and safety. Exploratory end points were investigator-assessed ORR in patients with baseline CNS metastases and relationship between circulating biomarkers and response.

Results: In total, 2219 patients were screened and blood-based NGS yielded results in 98.6% of the cases. Of these, 119 patients (5.4%) had ALK-positive disease; 87 were enrolled and received alectinib. Median follow-up was 12.6 months (range: 2.6-18.7). Confirmed ORR was 87.4% (95% confidence interval [CI]: 78.5-93.5) by investigator and 92.0% (95% CI: 84.1-96.7) by independent review facility. Investigator-confirmed 12-month duration of response was 75.9% (95% CI: 63.6-88.2). In 35 patients (40%) with baseline CNS disease, investigator-assessed ORR was 91.4% (95% CI: 76.9-98.2). Median PFS was not reached; 12-month investigator-assessed PFS was 78.4% (95% CI: 69.1-87.7). Safety data were consistent with the known tolerability profile of alectinib.

Conclusions: These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC.