On April 18, 2018, AstraZeneca announced that the U.S. Food and Drug Administration (FDA) had approved osimertinib for first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC).
These patients have tumors confirmed by FDA-approved testing to have epidermal growth factor receptor (EGFR) mutations (exon 19 deletion or exon 21 L858R mutation). This approval is based on results from the Phase III FLAURA trial, which were presented at the 2017 European Society for Medical Oncology Congress and published in the *New England Journal of Medicine*.
“FDA approval of osimertinib for first-line treatment is an exciting milestone for both patients and our company,” said Dave Frederickson, Executive Vice President and Head of Oncology at AstraZeneca. “Osimertinib demonstrated unprecedented median progression-free survival data across all pre-specified patient subgroups, including those with and without central nervous system metastases, and holds promise for extending the lives of more patients while halting tumor growth or spread.”
The principal investigator of the FLAURA trial, from the Winship Cancer Research Center at Emory University in Atlanta… Dr. Suresh S. Rama Lingam of the institute stated, "The approval of osimertinib for first-line treatment is a significant advancement in the treatment of EGFR-mutant patients and a major shift in treatment paradigms. Compared to previous-generation EGFR inhibitors, osimertinib has shown a significant improvement in progression-free survival without any unexpected safety signals."
Clinical Studies of Osimertinib
Safety data for osimertinib in the FLAURA trial were consistent with those observed in previous clinical trials. Osimertinib was generally well-tolerated, with 34% of patients receiving osimertinib experiencing grade 3 or higher adverse events (AEs), compared to 45% in the control group. Among patients treated with osimertinib, the most common adverse reactions (≥20%) were diarrhea (58%), rash (58%), dry skin (36%), nail toxicity (35%), stomatitis (29%), fatigue (21%), and decreased appetite (20%).
In the United States, osimertinib is approved for second-line treatment of patients with metastatic EGFR-mutant non-small cell lung cancer who have progressed after or during first-line EGFR-TKI therapy and have a secondary T790M mutation confirmed by an FDA-approved test. In 2017, the U.S. FDA granted osimertinib Breakthrough Therapy Designation and Priority Review designation for first-line treatment.
Based on data from the FLAURA trial, osimertinib was first approved in Brazil on April 16, 2018, for first-line treatment of patients with metastatic EGFR-mutant non-small cell lung cancer.
Companion Diagnostic Approved Simultaneously
AstraZeneca, in collaboration with Roche Molecular Systems, developed the cobas® EGFR mutation assay v2 as a companion diagnostic for osimertinib. This diagnostic assay has also been approved as a tissue- or plasma-based assay for identifying EGFR-mutant non-small cell lung cancer (NSCLC) patients eligible for first-line osimertinib therapy, and for identifying EGFR-RT790M mutation-positive NSCLC patients whose disease has progressed after first-line EGFR-RTKI therapy.
