Transcript

Hi, I'm Dr Yasir Elamin, Assistant Professor of Thoracic Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas. I would like to discuss Abstract 9624 from the recent 2020 ASCO Annual Meeting titled, " BRIGHTSTAR: A pilot trial of LCT with brigatinib in tyrosine kinase inhibitor (TKI)-naïve ALK-rearranged advanced NSCLC."

ALK rearrangements are identified in approximately 5% of all lung adenocarcinomas. The current standard of care is an ALK tyrosine kinase inhibitor. We have 2 second-generation TKIs that are FDA-approved in the first-line setting, alectinib and brigatinib.

These TKIs result in a response rate of around 70% to 80% and a long median progression-free survival. Despite this impressive response rate, the vast majority of these responses are incomplete responses, leaving behind what we call residual disease, which is essentially composed of drug-tolerant cancer cells.

The hypothesis behind this abstract is that this subpopulation of residual disease may ultimately be the source of clinical progression. By eliminating or reducing residual disease, we may be able to delay the emergence of resistance and improve clinical outcomes.

In this study, patients are treated with brigatinib for 8 weeks, and then treated with LCT with radiation or surgery to the sites of residual disease. I think it's important to note that the study allowed any number of metastatic disease sites in contrast to many other LCT studies, where only oligometastatic disease is allowed.

Nineteen patients were involved with a response rate of 95% and a disease control rate of 100%. At the time of ASCO presentation, 17 patients had completed LCT, 12 had radiation, 3 had surgery, and 2 had radiation and surgery.

Notably, all patients completed LCT successfully, and there were no adverse events related to LCT itself. The rest of the adverse events were expected and consistent with the known brigatinib safety profile.

This study shows that the use of LCT in combination with brigatinib in ALK-rearranged lung cancer is safe and feasible.

The impact of LCT on clinical outcomes will require longer follow-up and perhaps further studies to be conducted in a randomized fashion.