Dr. Fidler on the Utility of Dacomitinib in EGFR-Mutant NSCLC

Mary J. Fidler, MD
Published: Monday, Dec 16, 2019



Mary J. Fidler, MD, associate professor, Rush University Medical Center, discusses the utility of dacomitinib (Vizimpro) in patients with EGFR-mutant non–small cell lung cancer.

Dacomitinib is a second-generation irreversible EGFR TKI that has shown superior progression-free survival and overall survival (OS) compared with a first-generation agent; however, the agent is a little more toxic, says Fidler. Approximately two-thirds of patients in the phase III ARCHER 1050 trial required dose reductions. In a follow-up analysis, investigators showed that patients who were able to maintain the full dose of dacomitinib had less blood levels, suggesting a relationship between tolerability and metabolism. Notably, dose reductions were not associated with inferior outcomes, adds Fidler. 

Since dacomitinib is not designed to target T790M, it could be used up front. If patients develop an EGFR T790M mutation, they could receive osimertinib (Tagrisso) in the second-line setting. However, according to data from the phase III FLAURA trial, the median OS of osimertinib in the frontline setting was 38.6 months versus 31.8 months with erlotinib (Tarceva) or gefitinib (Iressa). Although approximately 30% of patients in both arms were not able to receive second-line therapy, it has become the preferred frontline therapy. However, the optimal role of dacomitinib has yet to fully defined, concludes Fidler.
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Mary J. Fidler, MD, associate professor, Rush University Medical Center, discusses the utility of dacomitinib (Vizimpro) in patients with EGFR-mutant non–small cell lung cancer.

Dacomitinib is a second-generation irreversible EGFR TKI that has shown superior progression-free survival and overall survival (OS) compared with a first-generation agent; however, the agent is a little more toxic, says Fidler. Approximately two-thirds of patients in the phase III ARCHER 1050 trial required dose reductions. In a follow-up analysis, investigators showed that patients who were able to maintain the full dose of dacomitinib had less blood levels, suggesting a relationship between tolerability and metabolism. Notably, dose reductions were not associated with inferior outcomes, adds Fidler. 

Since dacomitinib is not designed to target T790M, it could be used up front. If patients develop an EGFR T790M mutation, they could receive osimertinib (Tagrisso) in the second-line setting. However, according to data from the phase III FLAURA trial, the median OS of osimertinib in the frontline setting was 38.6 months versus 31.8 months with erlotinib (Tarceva) or gefitinib (Iressa). Although approximately 30% of patients in both arms were not able to receive second-line therapy, it has become the preferred frontline therapy. However, the optimal role of dacomitinib has yet to fully defined, concludes Fidler.

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