Dr. Horn on Monitoring Response and Resistance to Ensartinib in ALK+ NSCLC

Leora Horn, MD, MSc, associate professor of cancer research, Vanderbilt University Medical Center, discusses the use of circulating tumor DNA analysis as a means to monitor response to, as well as resistance to, ensartinib in patients with ALK—positive non–small cell lung cancer.

The study involved a cohort of patients from the phase II eXalt2 study (NCT01625234) of ensartinib. In 76 enrolled patients, all determined to have ALK-positive disease by fluorescence in situ hybridization, Horn and her colleagues assessed DNA from plasma samples for commonly occurring mutations using a panel of probes developed in collaboration with Resolution Biosciences. A total of 56 patients had genomic alterations detected by next-generation sequencing (NGS), and of those, 80% had ALK rearrangements.

Importantly, 5 patients with ALK-positive disease in their tissue samples did not show ALK positivity via NGS, which suggests that NGS may miss some patients who have ALK-positive disease, given that 4 of those patients responded to ensartinib. Furthermore, different responses to ensartinib were noted by variant; patients with variant 1 had better response and progression-free survival to ensartinib than did patients with variant 3.

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