The FDA has approved osimertinib (Tagrisso, AstraZeneca) for the first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or exon 21 L858R mutations), as detected by an FDA-approved test. The approval is based on results from the phase 3 FLAURA trial, which were presented at the European Society of Medical Oncology 2017 Congress and published in the New England Journal of Medicine.
Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA trial, from Winship Cancer Institute of Emory University, Atlanta, said: “The approval of osimertinib (Tagrisso) in the first-line setting represents a major advance in the treatment of patients with EGFR mutations and a significant change in the treatment paradigm. Osimertinib (Tagrisso) provides robust improvements in progression-free survival with no unexpected safety signals compared to the previous generation of EGFR inhibitors.”
The FLAURA trial compared osimertinib to current first-line EGFR tyrosine kinase inhibitors (TKIs), erlotinib (Tarceva, OSI Pharmaceuticals) or gefitinib (Iressa, AstraZeneca), in previously untreated patients with locally advanced or metastatic EGFR-mutated (EGFRm) NSCLC. Osimertinib met the primary endpoint of progression-free survival (PFS). PFS results with osimertinib were consistent across all prespecified patient subgroups, including in patients with or without central nervous system metastases. Overall survival data were not mature at the time of the final PFS analysis.
Safety data for osimertinib in the FLAURA trial were in line with those observed in prior clinical trials. Osimertinib was generally well tolerated, with grade 3 or higher adverse events occurring in 34% of patients taking osimertinib and 45% in the comparator arm. The most common adverse reactions (at an incidence of 20% or greater) in patients treated with osimertinib were diarrhea (58%), rash (58%), dry skin (36%), nail toxicity (35%), stomatitis (29%), fatigue (21%), and decreased appetite (20%).
In the U.S., osimertinib is already approved for the second-line treatment of patients with metastatic EGFRm NSCLC whose disease has progressed on or after a first-line EGFR-TKI therapy and who have developed the secondary T790M mutation, as detected by an FDA-approved test. In 2017, osimertinib was granted breakthrough therapy and priority review designations by the FDA in the first-line treatment setting.
AstraZeneca partnered with Roche Molecular Systems to develop the cobas EGFR Mutation Test v2 as the companion diagnostic for osimertinib. The diagnostic is simultaneously approved as a tissue- or plasma-based test to identify patients with EGFRm NSCLC who are eligible for first-line treatment with osimertinib and as a tissue or plasma-based test to identify patients with EGFR T790M mutation-positive NSCLC whose disease has progressed on a first-line EGFR TKI.
Source: AstraZeneca; April 18, 2018.