University of Colorado Cancer Center, Others, Show Brigatinib First Drug to Offer Over 1-year Control of ALK-Positive Lung Cancer Post-Crizotinib

D. Ross Camidge, MD, PhD

The duration of this benefit appears to be significantly longer.

About 3-5 percent of lung cancers are caused by changes in the gene ALK. In 2011, the FDA granted accelerated approval for the drug crizotinib to target these ALK changes. However, two major problems have remained: Crizotinib does not pass into the brain and so is unable to target ALK-positive lung cancer in the central nervous system, and the genetic diversity of cancer allows the later growth of subpopulations that can resist the drug, leading to renewed growth. In response, researchers have been actively developing next-generation ALK-inhibitors.

Results of a multi-center, 222-person phase 2 clinical trial of the next-generation ALK inhibitor, brigatinib at 180mg/day, used after failure of crizotinib showed a 54 percent response rate and 12.9 month progression-free survival. (Effects were lower at a lower dose.) Results are published in the Journal of Clinical Oncology.

“What brigatinib at this higher dose shows is comparable response rates to other next generation ALK inhibitors post-crizotinib but – and this is important – the duration of this benefit appears to be significantly longer,” says D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the CU Cancer Center and director of Thoracic Oncology at the CU School of Medicine. Camidge is the paper’s senior author.

In fact, Camidge points out that at the time of publication, many patients enrolled on this trial continued to experience cancer control and that more recent results presented at academic conferences show that median progression-free survival with brigatinib against ALK-positive lung cancer may be closer to 16 months.

“Once a cancer resists…

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