Osimertinib in patients with T790M mutation‐positive, advanced non–small cell lung cancer: Long‐term follow‐up from a pooled analysis of 2 phase 2 studies

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Osimertinib is a third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is selective for both EGFR‐TKI–sensitizing and T790M (threonine‐to‐methionine substitution at codon 790)‐resistance mutations. The authors present long‐term follow‐up data from a preplanned, pooled analysis of phase 2 studies, the AZD9291 First Time in Patients Ascending Dose Study (AURA) extension trial (clincialtrials.gov identifier NCT01802632) and the AURA2 trial (NCT02094261).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients with centrally confirmed, T790M mutation‐positive, advanced non‐small cell lung cancer received osimertinib 80 mg once daily until disease progression or study discontinuation. Response was assessed by a blinded, independent, central review using Response Evaluation Criteria in Solid Tumors, version 1.1. The primary endpoint was the objective response rate.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In total, 411 patients received osimertinib (second line, 129 patients; third line or later, 282 patients). At the data cutoff date of November 1, 2016, the median treatment exposure was 16.4 months (range, 0‐29.7 months), the objective response rate was 66% (95% confidence interval [CI], 61%‐70%), the median response duration was 12.3 months (95% CI, 11.1‐13.8 months), and the median progression‐free survival was 9.9 months (95% CI, 9.5‐12.3 months). At the data cutoff date of May 1, 2018, 271 patients (66%) had died, and 140 patients (34%) had discontinued before death. The median overall survival was 26.8 months (95% CI, 24.0‐29.1 months); and the 12‐month, 24‐month, and 36‐month survival rates were 80%, 55%, and 37%, respectively. Grade ≥3 possibly causally related (investigator assessed) adverse events were reported in 65 patients (16%), and the most common were rash (grouped terms; 42%; grade ≥3, 1%) and diarrhea (39%; <1%).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>This pooled analysis represents the most mature clinical trial data for osimertinib in patients with pretreated, T790M‐positive, advanced non‐small cell lung cancer, further establishing osimertinib as a standard of care for this patient population.</jats:p></jats:sec>