New TKI May Benefit NSCLC Patients With EGFR Mutation

There may soon be a new first-line treatment option for patients with locally advanced or metastatic EGFR mutation–positive non–small-cell lung cancer (NSCLC). On July 27, AstraZeneca announced that first-line osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has demonstrated a statistically significant and clinically meaningful progression-free survival benefit in EGFR mutation–positive NSCLC compared with current standard-of-care treatment.

The company reported on the phase III FLAURA trial, which showed that osimertinib may be superior to the current standard first-line therapies erlotinib and gefitinib in previously untreated patients with locally advanced or metastatic EGFR mutation–positive NSCLC.

“The strong results from the FLAURA trial are very exciting news for patients with EGFR mutation–positive NSCLC, providing physicians with a potential new first-line treatment option to improve outcomes in this disease,” said Sean Bohen, MD, PhD, executive vice president of global medicines development and chief medical officer at AstraZeneca in San Francisco, California.

FLAURA assessed the efficacy and safety of osimertinib 80 mg once daily vs either erlotinib 150 mg orally once daily or gefitinib 50 mg orally once daily. All the patients were previously untreated with locally advanced or metastatic EGFR mutation–positive NSCLC. The trial was a double-blinded randomized study, with 556 patients from 30 countries.

Bohen said that AstraZeneca will now be initiating discussions with global health authorities on the data and pursuing regulatory submissions. Osimertinib is designed to inhibit both EGFR-sensitizing and EGFR T790M resistance mutations. This agent also has clinical activity against central nervous system (CNS) metastases. Approximately half of patients develop resistance to approved EGFR TKIs such as gefitinib and erlotinib due to the T790M resistance mutation.

The efficacy, safety, and tolerability profiles for osimertinib, erlotinib, and gefitinib in the trial were consistent with what has been previously reported with these agents, according to the company. A full evaluation of the FLAURA data is ongoing, and further results will be presented at an upcoming medical meeting. “A high-level readout and detailed results are not available at this time,” a spokesperson for AstraZeneca told OncoTherapy Network.

It is hoped that osimertinib can help address a significant unmet clinical need. Approximately 25% of patients with EGFR mutation–positive NSCLC have brain metastases at diagnosis, increasing to approximately 40% within 2 years of diagnosis. Osimertinib is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.