The FDA has granted approval to AstraZeneca's Tagrisso (osimertinib) for the treatment of adult patients with unresectable Stage III epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy. This approval marks a significant advancement in the treatment landscape for this specific subset of lung cancer patients.
The approval was based on the results of the Phase III LAURA trial, a randomized, double-blind, placebo-controlled, multi-center, global study. The 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 80 mg once-daily oral tablets until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Patients in the placebo arm were offered Tagrisso upon progression.
Efficacy of Tagrisso in LAURA Trial
The LAURA trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients treated with Tagrisso compared to placebo. Tagrisso 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). The median PFS for patients treated with Tagrisso was 39.1 months, compared to 5.6 months for those on placebo.
While overall survival (OS) data were not mature at the time of the analysis, the trial continues to assess OS as a secondary endpoint. No trend towards a detriment had been observed.
Addressing Unmet Needs in EGFR-Mutated NSCLC
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), which block the cell-signaling pathways that drive tumor cell growth.
"The approval of Tagrisso for patients with Stage III, unresectable EGFR-mutated non-small cell lung cancer addresses a critical need for patients with these mutations who have never had the option of targeted therapy before," said Dave Fredrickson, EVP, Oncology Business Unit, AstraZeneca. "The results of the LAURA trial show the powerful impact Tagrisso can make as backbone therapy in this disease, and with this approval, patients across all stages of EGFR-mutated non-small cell lung cancer can now benefit."
Safety Profile
The safety profile of Tagrisso in the LAURA trial was consistent with its established profile. Common adverse events occurring in at least 20% of patients included lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.
Tagrisso's Expanding Role in Lung Cancer Treatment
Tagrisso is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. It is now approved for use in the first-line metastatic setting as a monotherapy, in combination with chemotherapy, and as an adjuvant treatment for early-stage disease.
AstraZeneca is also investigating Tagrisso in the neoadjuvant setting in the NeoADAURA Phase III trial and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial. The company is also researching ways to address tumor mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso plus savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.
