BRIGHTSTAR: Local Consolidative Therapy with Brigatinib in Tyrosine Kinase Inhibitor-Naïve ALK-Rearranged Metastatic NSCLC

Expert oncologist Yasir Elamin, MD, shares data from the BRIGHTSTAR trial and considers how it may inform real-world use of brigatinib in patient with ALK-rearranged metastatic non–small cell lung cancer.

BRIGHTSTAR: Local Consolidative Therapy with Brigatinib in Tyrosine Kinase Inhibitor-Naïve ALK-Rearranged Metastatic NSCLC

Background

  • ALK tyrosine kinase inhibitors (TKIs) are now the standard of care for patients with ALK-rearranged metastatic NSCLC with impressive response rates in the first line setting
  • Approximately 95% of patients who have an initial response to ALK-TKIs exhibit an incomplete response resulting in residual disease that may enable the emergence of acquired resistance
  • Minimizing or eliminating residual disease with local consolidation therapy (LCT) may delay the development of resistance and improve clinical outcomes

Study Design

  • Patient population had TKI-naïve ALK+ advanced NSCLC
    • Over 18 years of age
    • Documented ALK rearrangement (tissue or liquid biopsy)
    • TKI naïve or first-line brigatinib within ≤ 8 weeks of enrollment
    • At least one site of residual disease for LCT
    • ECOG PS ≤ 2
  • Patients received brigatinib until disease progression or unacceptable toxicity
  • Non-PD patients received local consolidative therapy, stratified by active sites of disease to LCT to all sites or LCT to sites at physician discretion

Objectives

  • Primary objective was safety and tolerability of brigatinib with LCT
  • Secondary objectives included PFS, OS, and TTP on non-LCT lesions
  • Exploratory Objectives included utility of pretreatment, pre-LCT and post-LCT liquid biopsy assessment as a prognostic and predictive biomarker

Results/Conclusions

  • Brigatinib with LCT is safe in patients with ALK-rearranged advanced NSCLC
  • Brigatinib with LCT yielded promising outcomes when compared to historical outcomes: 3-year PFS rate was 66% in Brightstar compared to 47% in the brigatinib arm of ALTA-1L
  • Complete LCT, baseline ALK plasma negativity, and lower post-induction volume, but not number of metastases at baseline (oligo vs poly) were associated with increased benefit for LCT
  • A randomized trial (BrightStar-2) is planned to compare two intensifications strategies, LCT and chemotherapy, with brigatinib alone as first line therapy for ALK+ NSCLC