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

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

Patient population had TKI-naïve ALK+ advanced NSCLC

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

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

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

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

Videos

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 

Yasir Y. Elamin, MD, assistant professor, Department of Thoracic/Head & Neck Medical Oncology, the Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the efficacy of poziotinib in patients with 

exon 20–mutated non–small cell lung cancer (NSCLC) with near-loop vs far-loop mutations.

A phase 2 study (NCT03066206) investigated the efficacy and safety of poziotinib in this population. The agent showed a 32.0% confirmed objective response rate (ORR) in the entire study population.

The phase 2 study focused on mutation insertion location in order to understand why some patients responded to poziotinib while others progressed, Elamin says. The response rate was 46% in patients with near-loop mutations, whereas no patients with far-loop mutations responded, Elamin notes.

Additionally, the median progression-free survival (PFS), as well as 6-month and 12-month PFS rates, displayed a trend toward better outcomes in patients with near-loop mutations, Elamin explains. Ba/F3 cells in preclinical models further supported these findings, confirming that patients with near-loop mutations are more sensitive to poziotinib, and that insertion location affects the activity and efficacy of the drug in these mutations, Elamin concludes.

Yasir Y. Elamin, MD, discusses the efficacy of poziotinib in patients with EGFR exon 20–mutated non–small cell lung cancer with near-loop vs far-loop mutations.

Dr. Elamin on Poziotinib Efficacy and Mutation Insertion Location in NSCLC

Yasir Y. Elamin, MD, assistant professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses 

 fusions result from the fusion of the NRG gene with an additional partner gene. However, they are rare, occurring in approximately 0.2% of all solid tumors, Elamin says. 

 fusions are enriched in a mucinous adenocarcinoma of the lung and 

 wild-type pancreatic adenocarcinoma, Elamin adds. The NRG fusion protein binds to the HER3 protein on the surface of the cancer cell, causing downstream signaling and activating other pathways, Elamin explains.

 fusions, extensive clinical research remains a relatively new endeavor, Elamin continues. However, based on limited retrospective studies, patients with 

 fusions may not be as responsive to traditional chemotherapy and immunotherapy, limiting the treatment options in the metastatic setting, Elamin explains.

 fusion is through RNA-based sequencing. Since the intronic region in the fused gene is large, it is easier to detect 

 fusions using an RNA-based sequencing platform, Elamin concludes.

Yasir Y. Elamin, MD, discusses NRG1 fusions in solid tumors.


Yasir Y. Elamin, MD

Articles

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

Dr. Elamin on Poziotinib Efficacy and Mutation Insertion Location in NSCLC

Dr. Elamin on NRG1 Fusions in Solid Tumors