AstraZeneca's Osimertinib on Track for First-Line Treatment of NSCLC With a Specific Mutation

AstraZeneca’s epidermal growth factor receptor (EGFR) inhibitor, osimertinib (Tagrisso), is on the fast track in 2018 to become a first-line treatment for adult patients with locally-advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR mutations.

The drug was approved by the FDA in 2015 as a second-line treatment for patients with T790M-mutated NSCLC who have regressed following treatment with other EGFR inhibitors.

Last month, AstraZeneca announced that the FDA has accepted and granted priority review to its supplemental new drug application (sNDA) for the label expansion. The drug also received breakthrough therapy designation for this indication in October 2017.

The expanded indication follows positive results from the phase III FLAURA trial, in which Tagrisso significantly improved progression-free survival (PFS) compared to erlotinib or gefitinib in previously-untreated patients. It also had a lower rate of adverse events. In the double-blind trial, 556 patients were randomly assigned to receive either osimertinib (at a dose of 80 mg once daily), gefitinib (at a dose of 250 mg once daily) or erlotinib (at a dose of 150 mg once daily).

Median PFS was significantly longer with osimertinib (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% CI, 0.37 to 0.57; P <0.001).

Writing in an editorial about these results in the January 11, 2018, issue of the New England Journal of Medicine, Sanjay Popat, FRCP, PhD, an oncologist at the Royal Marsden in London, posed several thoughts about whether or not osimertinib should be considered the new standard for this type of NSCLC.

Among the factors he cited: The FLAURA trial cannot yet evaluate overall survival. In addition, FLAURA data on the activity of osimertinib in patients who had metastases to the nervous system are still out. Further, it is not yet understood which patients will develop resistance to first-line osimertinib.

Another trial, AURA3, is currently active, evaluating osimertinib as a second-line therapy in patients who were already treated with erlotinib or gefitinib. Those results will set a key benchmark for second-line osimertinib, he wrote. Using osimertinib after first-line afatinib or dacomitinib instead may improve overall survival further, given the superiority of afatinib or dacomitinib over gefitinib, although with more adverse events.

However, he called the PFS results “profoundly impressive,” noting it has fewer adverse events and “has activity in [central nervous system] disease that is superior to that of the other available” drugs and called it an “ideal first-line choice for EGFR-mutated NSCLC.”