Osimertinib is safe and effective in patients who progressed on an EGFR tyrosine kinase inhibitor.

  • Major finding: Osimertinib is safe and effective in patients who progressed on an EGFR tyrosine kinase inhibitor.

  • Approach: An open-label phase II trial tested osimertinib safety and activity in patients with EGFRT790M NSCLC.

  • Impact: Patients who have acquired resistance to EGFR tyrosine kinase inhibitors may respond to osimertinib.

Patients with EGFR-mutant non–small cell lung cancer often respond well to first-line EGFR tyrosine kinase inhibitors (TKI). However, TKI resistance often develops, which in approximately half of patients is due to acquisition of the EGFRT790M resistance mutation. Osimertinib is an oral irreversible EGFR TKI that has activity against EGFRT790M as well as other TKI-sensitizing mutations, and preliminary clinical data indicate that it has activity in patients with advanced EGFRT790M-positive NSCLC. In a multicenter, open-label, single-arm phase II trial, Goss and colleagues evaluated the safety and efficacy of osimertinib in 210 patients with EGFRT790M-positive NSCLC who had progressed after therapy with an EGFR TKI. The primary endpoint was the proportion of patients who achieved an objective response, and secondary endpoints included progression-free survival, safety, and duration of response. Of the 199 evaluable patients, 140 (70%) had an objective response, including 6 (3%) complete responses. The median duration of response was 11.4 months, and 50% of patients had progressed or died by the data cutoff. The median progression-free survival was 9.9 months. Osimertinib had a manageable toxicity profile, with adverse events leading to treatment discontinuation in 5% of patients. Serious adverse events occurred in 25% of patients, including one likely treatment-related death due to interstitial lung disease. Altogether, the results of this study suggest that osimertinib is effective and has manageable side effects as a single-agent therapy in patients with EGFRT790M-positive NSCLC that has progressed after treatment with other EGFR TKIs. Further, patient selection for osimertinib treatment may be guided by EGFRT790M mutation status.

Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, et al. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 2016 Oct 14 [Epub ahead of print].

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