The US Food and Drug Administration (FDA) has approved osimertinib for the 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours 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 III FLAURA trial, which were presented at the European Society of Medical Oncology 2017 Congress and published in the New England Journal of Medicine.

In 2017, osimertinib was granted Breakthrough Therapy and Priority Review designations by the US FDA in the 1st-line treatment setting.

Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA trial, from Winship Cancer Institute of Emory University, Atlanta, said “The approval of osimertinib in the 1st-line setting represents a major advance in the treatment of patients with EGFR mutations and a significant change in the treatment paradigm. Osimertinib 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 1st-line EGFR tyrosine kinase inhibitors (TKIs), erlotinib or gefitinib, in previously-untreated patients with locally-advanced or metastatic EGFR-mutated (EGFRm) NSCLC.

Osimertinib met the primary endpoint of progression-free survival (PFS), with a median PFS of 18.9 months compared to 10.2 months in the TKI arm.

PFS results were consistent across all pre-specified patient subgroups, including in patients with or without central nervous system (CNS) metastases.

Overall survival data were not mature at the time of the final PFS analysis.

Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit at AstraZeneca, said “Today’s FDA approval of osimertinib in the 1st-line setting is an exciting milestone for patients and our company. Osimertinib delivered unprecedented median progression-free survival data across all pre-specified patient subgroups, including patients with or without CNS metastases, and could prolong the lives of more patients without their tumours growing or spreading.”

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 (AEs) occurring in 34% of patients taking osimertinib and 45% in the comparator arm.

The most common adverse reactions (≥20%) in patients treated with osimertinib were diarrhoea (58%), rash (58%), dry skin (36%), nail toxicity (35%), stomatitis (29%), fatigue (21%) and decreased appetite (20%).

Source: AstraZeneca