Dr. Shum on Mechanisms of Resistance in Oncogene-Driven NSCLC

Elaine Shum, MD
Published: Tuesday, Feb 19, 2019



Elaine Shum, MD, medical oncologist, NYU Langone’s Perlmutter Cancer Center, discusses mechanisms of resistance in patients with oncogene-driven non–small cell lung cancer (NSCLC).

Based on data from the phase III FLAURA and ALEX studies, osimertinib (Tagrisso) and alectinib (Alecensa) have become the recommended frontline treatments for patients with EGFR-mutant and ALK-positive NSCLC, respectively. Physicians are still learning why tumors develop mechanisms of resistance, says Shum. Although there is no substantial insight into why this occurs, there is reason to believe that these targeted agents isolate a clone and allow for another clone to drive the disease undetected. Future studies involving more biopsies at the time of progression will hopefully shed more light on this issue, she adds.

For patients who have developed resistance to treatment, combination therapy with various TKIs may be a potential strategy, says Shum, although toxicity may become an issue. Additionally, some anecdotal studies have shown improved outcomes with an EGFR inhibitor and MET inhibitor in EGFR-mutant patients with MET amplification.
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Elaine Shum, MD, medical oncologist, NYU Langone’s Perlmutter Cancer Center, discusses mechanisms of resistance in patients with oncogene-driven non–small cell lung cancer (NSCLC).

Based on data from the phase III FLAURA and ALEX studies, osimertinib (Tagrisso) and alectinib (Alecensa) have become the recommended frontline treatments for patients with EGFR-mutant and ALK-positive NSCLC, respectively. Physicians are still learning why tumors develop mechanisms of resistance, says Shum. Although there is no substantial insight into why this occurs, there is reason to believe that these targeted agents isolate a clone and allow for another clone to drive the disease undetected. Future studies involving more biopsies at the time of progression will hopefully shed more light on this issue, she adds.

For patients who have developed resistance to treatment, combination therapy with various TKIs may be a potential strategy, says Shum, although toxicity may become an issue. Additionally, some anecdotal studies have shown improved outcomes with an EGFR inhibitor and MET inhibitor in EGFR-mutant patients with MET amplification.



View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Online Medical Crossfire®: 5th Annual Miami Lung Cancer ConferenceMay 30, 20196.5
Community Practice Connections™: Working Group for Changing Standards in EGFR-Mutated Lung Cancers: Real-World Applications of the Evidence for NursesJun 29, 20191.5
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