Dr. Liu on Sequencing Therapy in ALK-Positive NSCLC

Stephen Liu, MD
Published: Monday, Oct 01, 2018



Stephen Liu, MD, associate professor of medicine, Division of Hematology and Oncology, Georgetown University Medical Center, discusses sequencing strategies for patients with ALK-positive non–small cell lung cancer (NSCLC).

In the past, physicians relied on first-line crizotinib (Xalkori) for patients with ALK-positive disease. Moving alectinib (Alecensa) into the frontline setting resets everything, says Liu. Everything that was known about resistance needs to be redone because the resistance patterns and mechanisms were very different with crizotinib, he adds.

Early and mostly retrospective data have shown modest but greater than 0 response rates to brigatinib (Alunbrig) and ceritinib (Zykadia) following alectinib. Liu says that lorlatinib probably holds the most promise. Early studies have shown response rates upwards of 40% for patients who had received 2 or more ALK tyrosine kinase inhibitors.

As new agents develop that have continued central nervous system penetration and maintain their activity in the face of resistance, physicians will have more empiric therapies to use in the salvage setting. Additionally, mutation profiling may soon be used to select which drugs to use in the salvage setting, adds Liu.
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Stephen Liu, MD, associate professor of medicine, Division of Hematology and Oncology, Georgetown University Medical Center, discusses sequencing strategies for patients with ALK-positive non–small cell lung cancer (NSCLC).

In the past, physicians relied on first-line crizotinib (Xalkori) for patients with ALK-positive disease. Moving alectinib (Alecensa) into the frontline setting resets everything, says Liu. Everything that was known about resistance needs to be redone because the resistance patterns and mechanisms were very different with crizotinib, he adds.

Early and mostly retrospective data have shown modest but greater than 0 response rates to brigatinib (Alunbrig) and ceritinib (Zykadia) following alectinib. Liu says that lorlatinib probably holds the most promise. Early studies have shown response rates upwards of 40% for patients who had received 2 or more ALK tyrosine kinase inhibitors.

As new agents develop that have continued central nervous system penetration and maintain their activity in the face of resistance, physicians will have more empiric therapies to use in the salvage setting. Additionally, mutation profiling may soon be used to select which drugs to use in the salvage setting, adds Liu.

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