AstraZeneca's Tagrisso (osimertinib) has received approval from the European Commission for the treatment of adult patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations, and whose disease has not progressed during or following platinum-based chemoradiation therapy (CRT). This approval marks a significant advancement in the treatment landscape for this specific subset of NSCLC patients in the European Union.
The approval is based on the results of the Phase III LAURA trial, a randomized, double-blind, placebo-controlled, multi-center, global study. The trial demonstrated that Tagrisso significantly reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio 0.16; 95% confidence interval 0.10-0.24; p<0.001), as assessed by blinded independent central review. Patients treated with Tagrisso experienced a median progression-free survival (PFS) of 39.1 months, compared to 5.6 months for those receiving placebo.
Clinical Impact and Expert Commentary
"Today's approval marks a major breakthrough for patients in the EU with unresectable, EGFR-mutated non-small cell lung cancer, delivering the first targeted treatment in this setting," said Manuel Cobo, MD, Specialist Physician of the Medical Oncology Service at the Carlos Haya University Hospital, Malaga, Spain, and investigator for the trial. "Osimertinib reduced the risk of disease progression or death by an unprecedented 84 per cent in the LAURA trial, setting a new benchmark for outcomes and underscoring the importance of testing for EGFR mutations upon diagnosis."
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, added, "Tagrisso is now the first and only EGFR inhibitor and targeted treatment approved in the EU for locally advanced, unresectable lung cancer, providing a new standard of care to patients who have historically experienced early progression after chemoradiation therapy. The powerful results from the LAURA trial show Tagrisso improves outcomes for patients in the unresectable setting, reinforces the importance of timely EGFR testing and solidifies Tagrisso as the backbone therapy in EGFR-mutated non-small cell lung cancer."
Trial Details and Safety Profile
The LAURA trial enrolled 216 patients across more than 145 centers in over 15 countries, including the US, Europe, South America, and Asia. Patients were treated with Tagrisso 80mg once-daily oral tablets until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Upon progression, patients in the placebo arm were offered treatment with Tagrisso. The primary endpoint was PFS, and the trial is ongoing to assess the secondary endpoint of overall survival (OS).
The safety and tolerability of Tagrisso in the LAURA trial were consistent with its established profile, and no new safety concerns were identified.
NSCLC and EGFR Mutations
Lung cancer is a significant global health concern, with an estimated 2.4 million people diagnosed each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases. Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia, have EGFR-mutated NSCLC. These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKIs), such as Tagrisso, which block the cell-signaling pathways that drive tumor cell growth.
Tagrisso's Expanding Role
This EU approval is the fifth major approval for Tagrisso based on the LAURA trial, following recent approvals in the US, Switzerland, South Korea, and Australia. Regulatory applications are also currently under review in China, Japan, and several other countries. Tagrisso is already approved as monotherapy in more than 100 countries, including the US, EU, China, and Japan, for various indications in NSCLC. It is also approved in combination with chemotherapy in the US, China, and several other countries for first-line treatment of patients with locally advanced or metastatic EGFR-mutated NSCLC.
