Results of a Phase 3 trial support the use of Tagrisso (osimertinib) as a new standard of care in the first-line treatment of patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).

Lung cancer accounts for roughly quarter of all cancer deaths, and NSCLC represents about 75 percent of lung cancers. EGFRm NSCLC accounts for 10 to 15 percent of NSCLC patients in the United States and Europe, and for 30-40 percent in Asia.

Doctors use EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, to treat these patients by targeting the affected cell signaling pathway. However, almost half of treated patients develop resistance to these drugs because of a secondary mutation (known as EGFR T790M), which leads to disease progression.

Tagrisso, an EGFR-TKI that inhibits EGFR T790M resistance mutation. Regulatory agencies in 50 countries including the United States, China, Japan and the 28-member European Union have approved its use to treat patients with EGFR T790M mutation-positive advanced NSCLC.

FLAURA is a Phase 3 clinical trial (NCT02296125) designed to compare the efficacy and safety of Tagrisso to either erlotinib or gefitinib (the current standard of care) in patients with locally advanced or metastatic EGFRm NSCLC.

AstraZeneca, the drug’s developer, presented results of the study — which involved 555 patients in 30 countries — at the recent European Society of Medical Oncology (EMSO) 2017 Congress in Madrid. it assessed the drug’s efficacy by monitoring several endpoints including progression-free survival (PFS) and duration of response.

Regarding PFS, patients treated with Tagrisso had 40 percent lower reduction in risk of progression or death compared to those treated with the other drugs — 18.9 versus 10.2 months. This included patients with and without metastasis in the central nervous system. Patients treated with Tagrisso also had a longer duration of response (17.2 months) than those treated with the other drugs (8.5 months).

Safety data of Tagrisso showed a low rate of adverse events such as diarrhea and dry skin. Overall, results support Tagrisso’s use as a new standard of care in first-line treatment of adult patients with locally advanced or metastatic EGFRm NSCLC.

“The FLAURA data are truly exciting,” Sean Bohen, AstraZeneca’s executive vice-president of global medicine development and chief medical officer, said in a press release. “Until now, even with the therapeutic advances offered by the first- and second-generation EGFR inhibitors, less than 20 percent of EGFR mutation-positive NSCLC patients survive for five years. The FLAURA data suggest early and sustained benefit with Tagrisso that has the potential to significantly impact long-term patient outcomes and help address the considerable unmet need that remains.”

Added Suresh S. Ramalingam of Atlanta’s Winship Cancer Institute at Emory University and FLAURA’s principal investigator: “The FLAURA data for osimertinib are likely to result in a major paradigm shift in the treatment of patients with EGFR mutation-positive advanced lung cancer. Not only did the trial demonstrate a robust improvement in efficacy with osimertinib when compared to other commonly-used EGFR inhibitors, the side effects profile was also more favourable with osimertinib.”

AstraZeneca is now discussing with global health authorities a regulatory submission for Tagrisso based on results from the FLAURA trial.