On April 19, 2018 The U.S. Food and Drug Administration (FDA) approved AstraZeneca’s Tagrisso (osimertinib) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) in tumors with epidermal growth factor receptor (EGFR) mutations (Press release, BioSpace, APR 19, 2018, View Source [SID1234525545]).
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The mutations, exon 19 deletions or exon 21 L858R mutations, will be detected by an FDA-approved test. The decision was based on data form the Phase III FLAURA clinical trial. Results were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress and published in the New England Journal of Medicine.
The FLAURA trial compared Tagrisso to current first-line EGFR tyrosine kinase inhibitors, erlotinib or gefitinib, in patients who had not received previous treatment for locally-advanced or metastatic EGFR-mutation NSCLC. It met the primary endpoint of progression-free survival, and were consistent across all pre-specified patient subgroups.
Patients receiving Tagrisso had about 18.9 months on average before the disease got worse compared to 10.2 months for patients receiving traditional treatments.
Tagrisso is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, with clinical activity against central nervous system cancers. It has been approved in the U.S. and Brazil for first-line EGFRm advanced NSCLC, and in more than 75 countries, including the U.S., Europe, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. It is also being evaluated as an adjuvant and in combination with other treatments.
It has also been approved in the U.S. for second-line treatment of patients with metastatic EGFRm NSCLC, whose disease has on or after a first-line EGFR-TKI round of therapy and who have developed the secondary T790 mutation. The drug received both Breakthrough Therapy and Priority Review designations from the FDA in 2017 for the first-line setting.
"Today’s FDA approval of Tagrisso in the first-line setting is an exciting milestone for patients and our company," said Dave Fredrickson, executive vice president, Head of the Oncology Business Unit at AstraZeneca, in a statement. "Tagrisso 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 tumors growing or spreading."
The drug is being evaluated in Europe and Japan as a first-line treatment, with regulatory decisions expected in the second half of this year. AstraZeneca has projected that Tagrisso could, at its peak, bring in $4 billion per year.
Lung cancer accounts for about one-fifth of all cancer deaths, more than breast, prostate and colorectal cancers combined. It is the leading cause of cancer death for both men and women. About 10 to 15 percent of patients in the U.S. and Europe and about 30 to 40 percent in Asia, have EGFRm NSCLC. They are especially sensitive to EGFR-TKI treatments, but those cancers typically develop resistance to that treatment, leading to disease progression.
"The approval of osimertinib 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," stated Suresh Ramalingam, principal investigator of the FLRUA trial, a researcher with the Winship Cancer Institute of Emory University in Atlanta. "Osimertinib provides robust improvements in progression-free survival with no unexpected safety signals compared to the previous generation of EGFR inhibitors."