The US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to osimertinib as first-line therapy for patients with metastatic epidermal growth factor receptor (EGFR)-positive non–small cell lung cancer (NSCLC).1
Tumors nearly always develop resistance to EGFR TKIs because of the EGFR T790M mutation. Osimertinib works by inhibiting both EGFR T790M and EGFR-sensitizing resistance mutations.
The FDA based its decision on evidence from the phase 3 FLAURA trial (ClinicalTrials.gov Identifier: NCT02296125), for which researchers randomly assigned 556 previously untreated patients with EGFR-positive NSCLC to receive osimertinib 80 mg once daily vs the standard of care.
The median progression-free survival (PFS) was 18.9 months vs 10.2 months for patients receiving osimertinib and standard care, respectively (hazard ratio [HR], 0.46; 95% CI, 0.37-0.57; P < .0001). A PFS benefit was observed in all subgroups.
Patients in the osimertinib arm had a longer median duration of response of 17.2 months vs 8.5 months in the standard care arm, and also had a greater overall response rate of 80% compared with 76% in standard care.
Overall survival (OS) trended in favor of osimertinib but was not statistically significant at time of data analysis. Median OS was not reached.
Osimertinib is currently approved as a second-line therapy for patients with NSCLC who progress after treatment with an EGFR TKI because of the EGFR T790M resistance mutation.
- Tagrisso granted breakthrough therapy designation by US FDA for the 1st-line treatment of patients with EGFR mutation-positive non-small cell lung cancer [news release]. AstraZeneca; October 9, 2017. https://www.astrazeneca.com/media-centre/press-releases/2017/tagrisso-granted-breakthrough-therapy-designation-by-us-fda-for-the-1st-line-treatment-of-patients-with-egfr-mutation-positive-non-small-cell-lung-cancer-09102017.html. Accessed October 10, 2017.