Dr. Pacheco on Second-Line Therapy for ALK+ NSCLC

Jose M. Pacheco, MD
Published: Tuesday, Aug 21, 2018



Jose M. Pacheco, MD, assistant professor, Medicine/Medical Oncology, Colorado University School of Medicine, discusses second-line therapy for patients with ALK-positive non–small cell lung cancer (NSCLC).

Following progression on a second-generation ALK inhibitor, Pacheco advises enrolling patients on a clinical trial with second-line brigatinib (Alunbrig). In the trial, patients will get a biopsy to determine what molecular markers they have that may help predict benefit from brigatinib following alectinib (Alecensa) or another second-generation ALK inhibitor, says Pacheco.

Physicians are gaining more insight into the mechanisms of resistance to ALK inhibitors. Physicians know that following a first-generation ALK inhibitor such as crizotinib (Xalkori), roughly 20% to 25% of patients may develop mutations in the ALK protein itself. Following a second-generation ALK inhibitor like ceritinib (Zykadia), alectinib, or brigatinib roughly 50% of patients will develop a mutation in the ALK protein that leads to resistance, says Pacheco.

Preclinically, it looks like lorlatinib may work better for a particular ALK mutation, G1202R. A patient in the phase II study of brigatinib who had a G1202R mutation responded to the tyrosine kinase inhibitor, says Pacheco. However, there have also been a lot of patients with G1202R mutations who have not responded to brigatinib. Physicians have limited data from lorlatinib in patients with that particular ALK mutation, explains Pacheco.


Jose M. Pacheco, MD, assistant professor, Medicine/Medical Oncology, Colorado University School of Medicine, discusses second-line therapy for patients with ALK-positive non–small cell lung cancer (NSCLC).

Following progression on a second-generation ALK inhibitor, Pacheco advises enrolling patients on a clinical trial with second-line brigatinib (Alunbrig). In the trial, patients will get a biopsy to determine what molecular markers they have that may help predict benefit from brigatinib following alectinib (Alecensa) or another second-generation ALK inhibitor, says Pacheco.

Physicians are gaining more insight into the mechanisms of resistance to ALK inhibitors. Physicians know that following a first-generation ALK inhibitor such as crizotinib (Xalkori), roughly 20% to 25% of patients may develop mutations in the ALK protein itself. Following a second-generation ALK inhibitor like ceritinib (Zykadia), alectinib, or brigatinib roughly 50% of patients will develop a mutation in the ALK protein that leads to resistance, says Pacheco.

Preclinically, it looks like lorlatinib may work better for a particular ALK mutation, G1202R. A patient in the phase II study of brigatinib who had a G1202R mutation responded to the tyrosine kinase inhibitor, says Pacheco. However, there have also been a lot of patients with G1202R mutations who have not responded to brigatinib. Physicians have limited data from lorlatinib in patients with that particular ALK mutation, explains Pacheco.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
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