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

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