Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples.

Osimertinib is a potent, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for EGFR-TKI sensitizing (EGFRm) and T790M resistance mutations. The primary objective of the cytology cohort in the AURA study was to investigate safety and efficacy of osimertinib in pretreated Japanese patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC), with screening EGFR T790M mutation status determined from cytology samples. The cytology cohort was included in the Phase I dose expansion component of the AURA study. Patients were enrolled based on a positive result of T790M by using cytology samples, and received osimertinib 80 mg in tablet form once daily until disease progression or until clinical benefit was no longer observed at the discretion of the investigator. Primary endpoint for efficacy was objective response rate (ORR) by investigator assessment. Twenty-eight Japanese patients were enrolled into the cytology cohort. At data cut-off (February 1, 2016), 12 (43%) were on treatment. Investigator-assessed ORR was 75% (95% confidence interval [CI] 55, 89) and median duration of response was 9.7 months (95% CI 3.8, not calculable [NC]). Median progression-free survival was 8.3 months (95% CI 4.2, NC) and disease control rate was 96% (95% CI 82, 100). The most common all-causality adverse events were paronychia (46%), dry skin (46%), diarrhea (36%) and rash (36%). Osimertinib provided clinical benefit with a manageable safety profile in patients with pretreated EGFR T790M mutation-positive NSCLC whose screening EGFR T790M mutation-positive status was determined from cytology samples. (ClinicalTrials.gov number NCT01802632).