Promising results have been reported from a phase 3 trial of osimertinib (Tagrisso, AstraZeneca) in the second-line treatment of patients with epidermal growth factor receptor (EGFR) T790M mutation-positive locally advanced or metastatic non–small-cell lung cancer (NSCLC). Second-line osimertinib was shown to significantly improve progression-free survival (PFS) compared with standard platinum-based doublet chemotherapy. The results were published online in the New England Journal of Medicine.
The AURA3 trial compared the efficacy and safety of osimertinib (80 mg once daily) with that of platinum-based doublet chemotherapy (platinum-pemetrexed) in 419 patients with EGFR T790M mutation-positive, locally advanced or metastatic NSCLC whose disease had progressed on or after treatment with a previous EGFR tyrosine kinase inhibitor (TKI). The study was conducted at more than 130 sites worldwide, including the United States, Canada, Europe, China, Japan, and Australia. The trial’s primary endpoint was PFS, and secondary endpoints included overall survival, the overall response rate, the duration of response, and the disease control rate.
Second-line osimertinib improved PFS by 5.7 months compared with standard platinum-based doublet chemotherapy (10.1 months vs. 4.4 months, respectively; hazard ratio [HR], 0.30; P < 0.001). Moreover, in the 34% of patients with central nervous system metastases at baseline, PFS was significantly greater with osimertinib than with platinum-based doublet chemotherapy (8.5 months vs. 4.2 months, respectively; HR, 0.32).
Grade-3 or greater drug-related adverse events (AEs) were reported in 6% of patients (n = 16) treated with osimertinib and in 34% (n = 46) of those treated with platinum-based doublet chemotherapy. The most common drug-related AEs included diarrhea (29%) and rash (28%) in the osimertinib group, and nausea (47%) and decreased appetite (32%) in the chemotherapy group.
Osimertinib 80 mg once daily is approved in the United States as first-line treatment for patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC.
Source: AstraZeneca; December 6, 2016.