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 MocciRajesh Patel, Zoe June Assaf, David S. Shames, Michael S. Mathisen, Shirish M. Gadgeel

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2040-2050
Number of pages11
JournalJournal of Thoracic Oncology
Volume16
Issue number12
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Alectinib
  • ALK-positive
  • Blood-based assay
  • Next-generation sequencing
  • NSCLC

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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