Tagrisso Demonstrates Significant Overall Survival Benefit in Phase III FLAURA Trial for First-Line Treatment of EGFR-Mutated NSCLC

Recently, AstraZeneca announced that its blockbuster third-generation EGFR inhibitor, Tagrisso (osimertinib), achieved positive results in a pivotal Phase 3 clinical trial for the treatment of previously untreated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations. The press release highlighted that Tagrisso is the first drug to demonstrate a statistically significant improvement in overall survival (OS) for these patients, and it also improves progression-free survival (PFS) in patients with central nervous system metastases.

Lung cancer is the most prevalent and deadliest cancer worldwide. It accounts for approximately 20% of all cancer-related deaths, with the number of fatalities from lung cancer exceeding the combined total of those from breast, prostate, and colorectal cancers! Lung cancer is broadly classified into two main categories: non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC comprising 80–85% of all lung cancer cases. Approximately 10–15% of NSCLC patients in the United States and Europe, and about 30–40% of Asian patients, harbor EGFR gene mutations in their tumors. Around 25% of NSCLC patients with EGFR mutations present with brain metastases at diagnosis, a proportion that rises to 40% within two years post-diagnosis. The occurrence of brain metastases reduces their median survival time to less than 8 months.

Over the past century, significant progress has been made in the treatment of lung cancer, and PD-1/PD-L1 inhibitors that have emerged in recent years have demonstrated substantial efficacy in lung cancer therapy. However, patients with non-small cell lung cancer (NSCLC) harboring EGFR gene mutations exhibit poor responses to immune checkpoint inhibitor therapy, whereas these patients are particularly sensitive to EGFR tyrosine kinase inhibitors.

AstraZeneca’s blockbuster anticancer drug, Tagrisso, is a third-generation, irreversible EGFR tyrosine kinase inhibitor. It inhibits EGFR activity in tumors harboring EGFR sensitizing mutations and the EGFR T790M resistance mutation, and has demonstrated clinical activity against central nervous system metastases. Tagrisso has been approved for marketing in more than 70 countries. In the United States, Japan, and the European Union, it has been approved as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR gene mutations. In China, it has been approved for second-line treatment of patients with advanced NSCLC harboring the EGFR T790M mutation. The application for Tagrisso as first-line treatment for NSCLC patients with EGFR gene mutations has been accepted by the China National Medical Products Administration (NMPA), with approval expected in the second half of this year.

In the randomized, double-blind, multicenter Phase 3 clinical trial named FLAURA, patients with non-small cell lung cancer (NSCLC) harboring EGFR gene mutations received treatment with Tagrisso or erlotinib/gefitinib. Erlotinib and gefitinib were the previous standard of care for these patients. Previous trial results had already demonstrated that Tagrisso significantly prolonged progression-free survival (PFS) compared to the active control group (18.9 months vs. 10.2 months, p<0.0001), but overall survival (OS) data were not yet mature. Today, AstraZeneca announced that Tagrisso met the OS clinical endpoint, delivering a statistically significant and clinically meaningful improvement in overall survival for patients. The company will present detailed OS results at future medical conferences.

Dr. José Baselga, Executive Vice President of Oncology R&D at AstraZeneca, stated, “The positive results announced today demonstrate that Tagrisso provides a significant survival benefit compared to previous standard treatments. This finding further confirms Tagrisso as the first-line standard of care for patients with metastatic NSCLC harboring EGFR mutations.”

References:

[1] TAGRISSO® (OSIMERTINIB) Significantly Improves Overall Survival in the Phase III FLAURA Trial for 1st-line EGFR-mutated Non-small Cell Lung Cancer. Retrieved August 9, 2019, from https://www.businesswire.com/news/home/20190809005184/en

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