Lung Cancer Drug Osimertinib (Tagrisso) Meets Primary Endpoint in Phase 3 Trial

First randomized study to evaluate EGFR T790M medication

The phase 3 AURA3 trial has met its primary endpoint, demonstrating superior progression-free survival (PFS) with osimertinib (Tagrisso, AstraZeneca) compared with standard platinum-based doublet chemotherapy as second-line treatment in patients with EGFR T790M mutation-positive, locally advanced or metastatic non–small-cell lung cancer (NSCLC) whose disease had progressed after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy. The trial involved more than 400 patients.

In addition to PFS, the objective response rate, disease control rate, and duration of response also showed clinically meaningful improvements compared with chemotherapy. 

Lung cancer is the leading cause of cancer death among both men and women, accounting for approximately one-third of all cancer deaths and more than breast, prostate, and colorectal cancers combined. Patients who have the EGFR mutation-positive form of NSCLC, which occurs in 10% to 15% of NSCLC patients in the United States and Europe, are particularly sensitive to treatment with currently available EGFR TKIs, which block the cell-signalling pathways that drive the growth of tumor cells. However, tumors almost always develop resistance to treatment, leading to disease progression. In approximately two-thirds of patients treated with approved EGFR TKIs, such as gefitinib (Iressa, AstraZeneca) and erlotinib (Tarceva, Genentech/Astellas Oncology), this resistance is caused by a secondary mutation, T790M.

The Tagrisso (osimertinib) 80-mg once-daily tablet is the first medication indicated for the treatment of adults with locally advanced or metastatic EGFR T790M mutation-positive NSCLC. Osimertinib is an irreversible EGFR inhibitor engineered to combat the mechanism of resistance by targeting the T790M resistance mutation.

Osimertinib is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without brain metastases, in those with leptomeningeal disease, and in combination with other treatments.

Source: AstraZeneca; July 18, 2016.