Sequencing Osimertinib in Patients With EGFR-Mutated NSCLC

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Aparna Hegde, MD, assistant professor of hematology/oncology at The University of Alabama at Birmingham, discusses the decision to use osimertinib (Tagrisso) in the frontline setting for treating patients with non–small cell lung cancer (NSCLC) who have EGFR mutations.

Hegde’s decision is based off results from the phase 3 FLAURA trial (NCT02296125) that compared osimertinib in the frontline setting against older EGFR tyrosine kinase inhibitors (TKIs) and found osimertinib to be superior. Progression-free survival (PFS) was significantly longer for patients on osimertinib at 18.9 months compared with 10.2 months in the TKI group (HR, 0.46; 95% CI, 0.37-0.57; P < .001).

Median duration of response was also longer in the osimertinib group at 17.2 months (95% CI, 13.8-22.0) with osimertinib vs 8.5 months (95% CI, 7.3-9.8) with standard EGFR TKIs. Moreover, recent results have shown an overall survival (OS) rate of 38.6% (95% CI, 34.5%- 41.8%) with osimertinib in this patient population.

According to Hegde, there are also challenges that come with osimertinib; once it’s used, patients can’t tolerate subsequent therapy. However, osimertinib is better tolerated in the frontline setting compared with older EGFR TKIs with adverse events of grade 3 or higher observed in 34% of patients compared to 45% in the TKI group. Therefore, Hegde says it’s best to use osimertinib as soon as possible in the frontline setting and give patients the best option first.

TRANSCRIPTION:

0:08 | In the metastatic setting, we've had results for quite some time now. The FLAURA trial showed a progression-free survival benefit with osimertinib compared to standard EGFR TKIs, or older EGFR TKIs. Based on those results, osimertinib was FDA approved in 2018 for first line use in patients with EGFR mutations in their metastatic NSCLC. We've known these results for a while, so we've been using this for a while.

In [treating] metastatic disease, I use osimertinib in the first-line setting, and I prefer to use osimertinib over other EGFR TKIs because it's more potent; it's more selective than older EGFR TKIs, and that's the reason why it's also better tolerated. Another reason is that a substantial proportion of patients who have disease progression after their first line of treatment are not able to receive any more treatments. We saw this in the FLAURA trial in both arms, as close to 30% of patients could not receive any subsequent therapy. So, it's important to use the best treatment at our disposal first, so that patients derive the most benefit they can.

1:26 | I always go with osimertinib in the first line setting, and you know, some people do use older EGFR TKIs in the first line setting, but it's not very well tolerated. Those older EGFR TKIs are not as potent and don't have good CNS [central nervous system] penetration, so patients tend to experience more CNS disease progression sooner, so I prefer to go with osimertinib first.