EU Recommends Approval of AstraZeneca's Tagrisso for Unresectable EGFR-Mutated NSCLC
核心洞察
The European Medicines Agency's CHMP has recommended Tagrisso (osimertinib) for EGFR (搜索)-mutated unresectable non-small cell lung cancer (搜索) (NSCLC (搜索)).
The recommendation is based on the LAURA Phase III trial, which demonstrated a significant reduction in disease progression or death compared to placebo.
Tagrisso reduced the risk of disease progression or death by 84% compared to placebo (HR 0.16; 95% CI 0.10-0.24; p<0.001).
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of AstraZeneca's Tagrisso (osimertinib) for adult patients with locally advanced, unresectable non-small cell lung cancer (搜索) (NSCLC (搜索)) whose tumors have epidermal growth factor receptor (EGFR (搜索)) exon 19 deletions or exon 21 (L858R) substitution mutations, and whose disease has not progressed during or following platinum-based chemoradiation therapy (CRT). This decision offers a new targeted treatment option for a subset of NSCLC patients with significant unmet needs.
LAURA Phase III Trial Results
The positive recommendation is based on the results of the LAURA phase III trial, which were published in The New England Journal of Medicine. The trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients treated with Tagrisso compared to placebo.
The data showed that Tagrisso reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio [HR] 0.16; 95% confidence interval [CI] 0.10-0.24; p<0.001) as assessed by blinded independent central review. The median PFS was 39.1 months in patients treated with Tagrisso versus 5.6 months for placebo, indicating a substantial increase in the time before disease progression. Overall survival (OS) data are still immature, and the trial continues to assess OS as a secondary endpoint.
Clinical Significance
Manuel Cobo, MD, Specialist Physician of the Medical Oncology Service at the Carlos Haya University Hospital, Malaga, Spain, and an investigator for the trial, emphasized the importance of these findings: “The LAURA results build on the established efficacy of osimertinib and support the approval of the first targeted therapy for patients with unresectable, EGFR (搜索)-mutated lung cancer. Today’s positive recommendation marks an important step towards offering patients in Europe a targeted treatment option that can extend the time before their disease progresses by more than three years.”
Current Landscape and Unmet Needs
Lung cancer remains a significant global health challenge, with over 450,000 people diagnosed each year in Europe alone. Non-small cell lung cancer (搜索) (NSCLC (搜索)) is the most common form of lung cancer, and among these patients, approximately 10-15% in Europe have tumors with an EGFR (搜索) mutation. Nearly one in five people with NSCLC has an unresectable tumor, highlighting the need for effective treatment options in this setting. Tagrisso's approval addresses a critical unmet need by providing a targeted therapy that has demonstrated significant efficacy in delaying disease progression.
Tagrisso: A Backbone Therapy
Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, stated, “Today’s news reinforces Tagrisso as the backbone therapy in EGFR (搜索)-mutated non-small cell lung cancer (搜索), meeting the critical unmet need for an effective targeted treatment option in the unresectable setting. Tagrisso has now demonstrated its benefit across all stages of EGFR-mutated lung cancer, representing a pivotal step in transforming care for patients who are urgently in need of innovative therapies that can help extend their lives.”
Trial Design and Patient Population
The LAURA trial is a randomized, double-blind, placebo-controlled, multi-center, global phase III trial involving patients with unresectable, Stage III EGFRm NSCLC (搜索) whose disease has not progressed following definitive platinum-based CRT. 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 trial enrolled 216 patients across more than 145 centers in over 15 countries, including the US, Europe, South America, and Asia.
The safety and tolerability of Tagrisso in the LAURA trial were consistent with its established profile, and no new safety concerns were identified.
Tagrisso's Expanding Role
Tagrisso (osimertinib) is a third-generation, irreversible EGFR (搜索)-TKI with proven clinical activity in NSCLC (搜索), including against central nervous system (CNS) metastases. It is already approved as monotherapy in more than 100 countries, including the US, EU, China, and Japan, for various indications, including 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC (搜索), locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFRm NSCLC. Tagrisso is also approved in combination with chemotherapy in the US, China, and several other countries for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC. AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC, including in the neoadjuvant and early-stage adjuvant resectable settings.