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