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Continued Emergence of Targeted Therapies for EGFR-Mutant NSCLC Underscores Importance of Molecular Testing

*July 2023*

With osimertinib (Tagrisso) available as a treatment option in both the metastatic and adjuvant settings for patients with EGFR-mutated non–small cell lung cpatients with EGFR-mutated non–small cell lung cancer ancer (NSCLC) and ongoing trials evaluating combination therapies for this patient population, molecular testing to identify these aberrations in patients with NSCLC remains critical, according to Pasi A. Jänne, MD, PhD.

“No patient should be left behind for EGFR mutation testing, either in the metastatic setting or in the adjuvant setting, because there are effective therapies for patients [in both settings]. If these therapies fail, understanding resistance is important. New therapeutic combinations are likely on the horizon, hopefully leading to further improvements in outcomes for this patient population with common EGFR-mutant NSCLC,” Jänne said in an interview with OncLive® during the 24th Annual International Lung Cancer Congress®.

In the interview, Jänne detailed his presentation on common EGFR mutations in NSCLC, touching on the importance of testing for EGFR mutations in all patients, the clinical implications of overall survival (OS) data for adjuvant osimertinib from the phase 3 ADAURA trial (NCT02511106), and ongoing trials examining combination therapies to potentially improve upon the use of single-agent osimertinib.

Jänne is a senior physician, director of the Lowe Center for Thoracic Oncology, director of the Belfer Center for Applied Cancer Science, and director of the Chen-Huang Center for EGFR Mutant Lung Cancers at Dana-Farber Cancer Institute, and a senior physician and professor of medicine at Harvard Medical School in Boston, Massachusetts.

OncLive: What was the primary focus of your presentation on common EGFR mutations in patients with NSCLC?

Jänne: Common EGFR mutations include exon 19 deletions and exon 21 L858R mutations, which account for about 85% of all EGFR mutations found in NSCLC. [In patients with these mutations], the standard of care is osimertinib in both the first-line metastatic setting and in the adjuvant setting.

I also highlighted some of the trials where we will have upcoming data over the next year, including the [phase 3] FLAURA2 [NCT04035486] and the MARIPOSA [NCT04487080] trials that aim to build on the single-agent use of a third-generation EGFR TKI to [evaluate] if [combination] therapies are better.

How should testing be conducted for EGFR mutations? Are they typically on reflex panels?

This varies a little bit from institution to institution. In general, they should be tested on reflex panels, and the standard of care is to test everyone’s cancer for an EGFR mutation. That includes surgical specimens as well because of the approval [of osimertinib] in the adjuvant setting.

If you can’t test from the tumor or the tumor biopsy is insufficient, then we test from a liquid biopsy. That would be the other way of doing this.

Looking at the phase 3 FLAURA trial (NCT02296125), what do mature data indicate about osimertinib’s use in the metastatic setting?

[These data] also demonstrate an improvement in OS over a prior generation of EGFR inhibitors. The other aspect of osimertinib that we as practicing clinicians are all happy about is the ability to penetrate the blood-brain barrier and treat central nervous system metastases. Therefore, having a pharmacological alternative to radiation is certainly welcome and has been for a while in this field. We look forward to the data on FLAURA2, which will come later on in 2023.

Could you expand on the design and objectives of the FLAURA2 and MARIPOSA trials, which could potentially put osimertinib’s role as standard frontline therapy into question?

FLAURA2 [evaluated] the combination of chemotherapy and osimertinib vs osimertinib [alone]. Chemotherapy [consisted of] carboplatin plus pemetrexed or cisplatin plus pemetrexed, so this was standard platinum-based chemotherapy added to osimertinib. The primary end point was progression-free survival, and a recent press release [stated] that the trial met its primary end point, and the data will be available later in 2023. Read more.