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The European Commission has approved Tagrisso (osimertinib; AstraZeneca) combined with pemetrexed and platinum-based chemotherapy for the first-line treatment of adult patients with advanced epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC) harboring exon 19 deletions or L858R mutations.

Lung cancer diagnoses in Europe exceed 450,000 annually.Approximately 10%-15% of patients with NSCLC in the US and Europe, and 30%-40% in Asia, have EGFR-mutated NSCLC.These patients are particularly responsive to treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs), which inhibit cell-signaling pathways that promote tumor growth.

Tagrisso, a third-generation, irreversible EGFR-TKI, has demonstrated significant clinical activity in NSCLC, including efficacy against central nervous system metastases. 

The European Commission approval follows the positive opinion of the European Medicines Agency's Committee for Medicinal Products for Human Use and is based on data from the phase 3 FLAURA2 trial published in The New England Journal of Medicine. 

FLAURA2 is a randomized, multicenter trial involving 557 adult patients with newly diagnosed locally advanced or metastatic NCSLC harboring an EGFR exon 19 deletion or L858R mutation who had not received prior systemic treatment for advanced disease. 

Patients were randomly assigned to receive 80 mg oral osimertinib once daily combined with chemotherapy (pemetrexed plus cisplatin or carboplatin) every 3 weeks for four cycles, followed by maintenance therapy with osimertinib and pemetrexed every 3 weeks; or oral osimertinib 80 mg once daily.

The primary endpoint is progression-free survival (PFS); the secondary endpoint of overall survival is still being assessed because the trial is ongoing.

Osimertinib plus chemotherapy reduced the risk for disease progression or death by 38% by investigator assessment compared with osimertinib monotherapy, the current first-line global standard of care (hazard ratio, 0.62; P <  .0001). Median PFS was 25.5 months for patients treated with osimertinib plus chemotherapy, an 8.8-month improvement over osimertinib monotherapy (16.7 months).

The PFS results from blinded independent central review were consistent with those by investigator assessment.

A trend toward an overall survival benefit was observed with osimertinib plus chemotherapy compared to osimertinib alone, as presented at the 2024 European Lung Cancer Congress. 

The safety profile of osimertinib combined with chemotherapy was consistent with the known profiles of the individual drugs. Adverse event (AE) rates were higher in the osimertinib plus chemotherapy arm and primarily consisted of well-characterized chemotherapy-related AEs. Discontinuation rates of osimertinib due to AEs were 11% for osimertinib plus chemotherapy and 6% for monotherapy. 

Tagrisso combined with chemotherapy is also approved in the US, China, Japan, and several other countries for the first-line treatment of patients with locally advanced or metastatic EGFR-mutated NSCLC. It is currently under review with global regulatory authorities for patients with unresectable, stage III EGFR-mutated NSCLC.