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Resistance to Osimertinib in EGFR-Mutated NSCLC

Insights From: Sai-Hong Ignatius Ou, MD, PhD, University of California, Irvine School of Medicine
Published: Tuesday, Jun 04, 2019



Transcript: 

Sai-Hong Ignatius Ou, MD, PhD: The resistance to osimertinib, whether it is used for T790M mutations or the upfront use of activating EGFR mutations, are actually very heterogeneous. You can have second-site EGFR T790M mutations—the C797S mutations. You could have MET amplifications. You could have small cell transformation. You could have lots of other bypass pathway activations. In a few cases, you actually get receptor tyrosine kinase fusions such as ALK fusions and RET fusions that can surface a secondary resistance mechanism. That is why regardless of how you use osimertinib, it’s important to get a biopsy on progression, preferably tissue. But if you have a good liquid biopsy that has a good panel that could detect the major genetic alterations—such as amplifications, mutations, and fusions—it’s highly recommended. It’s advisable to do that because of the risk of the heterogeneous mechanism of resistance of osimertinib.

The resistance mechanism from one of the Chinese studies is very similar to what has been published from the analysis of the AURA3 studies or the AURA17 studies. You see secondary-site mutations, you see MET amplifications, you see HER2 amplifications, and you see some other bypass pathway activations.

Transcript Edited for Clarity
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Transcript: 

Sai-Hong Ignatius Ou, MD, PhD: The resistance to osimertinib, whether it is used for T790M mutations or the upfront use of activating EGFR mutations, are actually very heterogeneous. You can have second-site EGFR T790M mutations—the C797S mutations. You could have MET amplifications. You could have small cell transformation. You could have lots of other bypass pathway activations. In a few cases, you actually get receptor tyrosine kinase fusions such as ALK fusions and RET fusions that can surface a secondary resistance mechanism. That is why regardless of how you use osimertinib, it’s important to get a biopsy on progression, preferably tissue. But if you have a good liquid biopsy that has a good panel that could detect the major genetic alterations—such as amplifications, mutations, and fusions—it’s highly recommended. It’s advisable to do that because of the risk of the heterogeneous mechanism of resistance of osimertinib.

The resistance mechanism from one of the Chinese studies is very similar to what has been published from the analysis of the AURA3 studies or the AURA17 studies. You see secondary-site mutations, you see MET amplifications, you see HER2 amplifications, and you see some other bypass pathway activations.

Transcript Edited for Clarity
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Working Group for Changing Standards in EGFR-Mutated Lung Cancers: Real-World Applications of the Evidence for NursesJun 29, 20191.5
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis SyndromeJun 30, 20191.0
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