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Second- and Third-Generation TKIs 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: In the United States, as I mentioned before, the FLAURA data have a large impact on how we practice treating EGFR-mutant non–small cell lung cancer. This is the first head-to-head trial of a third-generation versus a first-generation EGFR TKI [tyrosine kinase inhibitor] that has the highest progression-free survival, much better tolerability, and CNS [central nervous system] activity.

The ARCHER1050 is the dacomitinib versus gefitinib study. That trial excluded patients with a CNS metastasis, so it’s hard to judge what is the contribution or efficacy of patients with dacomitinib with CNS activity. Also, dacomitinib is administered at 45 mg once a day, which is the approved dose. Around 60% of the patients require dose reduction, and I think an additional 20% of these patients require 2 dose reductions. In terms of tolerability, it’s an issue with dacomitinib. If you do a cross-trial comparison of ARCHER1050 and FLAURA, osimertinib is better tolerated. Osimertinib has a longer progression-free survival, including for patients who have brain metastases. The outside real-world data is hard to supplant the data of the FLAURA study, in my opinion.

I think for the afatinib trial, the observation study and locations—either first-line, second-line, or third-line treatment—which is more of heterogeneous population—more of an adverse effect profile has been reported. Efficacy, I think, is similar to what has been reported, so numerically it’s less than what can be achieved with osimertinib. Again, it’s a personal preference. If they want to sequence, afatinib is a possibility followed by osimertinib, or clinicians can use upfront osimertinib.

Transcript Edited for Clarity
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Transcript: 

Sai-Hong Ignatius Ou, MD, PhD: In the United States, as I mentioned before, the FLAURA data have a large impact on how we practice treating EGFR-mutant non–small cell lung cancer. This is the first head-to-head trial of a third-generation versus a first-generation EGFR TKI [tyrosine kinase inhibitor] that has the highest progression-free survival, much better tolerability, and CNS [central nervous system] activity.

The ARCHER1050 is the dacomitinib versus gefitinib study. That trial excluded patients with a CNS metastasis, so it’s hard to judge what is the contribution or efficacy of patients with dacomitinib with CNS activity. Also, dacomitinib is administered at 45 mg once a day, which is the approved dose. Around 60% of the patients require dose reduction, and I think an additional 20% of these patients require 2 dose reductions. In terms of tolerability, it’s an issue with dacomitinib. If you do a cross-trial comparison of ARCHER1050 and FLAURA, osimertinib is better tolerated. Osimertinib has a longer progression-free survival, including for patients who have brain metastases. The outside real-world data is hard to supplant the data of the FLAURA study, in my opinion.

I think for the afatinib trial, the observation study and locations—either first-line, second-line, or third-line treatment—which is more of heterogeneous population—more of an adverse effect profile has been reported. Efficacy, I think, is similar to what has been reported, so numerically it’s less than what can be achieved with osimertinib. Again, it’s a personal preference. If they want to sequence, afatinib is a possibility followed by osimertinib, or clinicians can use upfront osimertinib.

Transcript Edited for Clarity
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