Osimertinib for Japanese patients with T790M‐positive advanced non‐small‐cell lung cancer: A pooled subgroup analysis

<jats:title>Abstract</jats:title><jats:p>Epidermal growth factor receptor (<jats:styled-content style="fixed-case">EGFR</jats:styled-content>)‐tyrosine kinase inhibitors (<jats:styled-content style="fixed-case">TKI</jats:styled-content>s) are the standard of care for non‐small‐cell lung cancer (<jats:styled-content style="fixed-case">NSCLC</jats:styled-content>) patients harboring EGFR mutations. However, almost all patients develop resistance after approximately 1 y of treatment, with >50% of cases due to the T790M secondary mutation of the EGFR gene. A large global Phase <jats:styled-content style="fixed-case">III</jats:styled-content> study (<jats:styled-content style="fixed-case">AURA</jats:styled-content>3) demonstrated that osimertinib significantly prolonged progression‐free survival (<jats:styled-content style="fixed-case">PFS</jats:styled-content>) over platinum‐doublet chemotherapy in patients with T790M‐positive <jats:styled-content style="fixed-case">NSCLC</jats:styled-content> who had progressed on previous <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content> therapy. However, it is not clear whether efficacy or safety of osimertinib in Japanese patients is similar to the overall population. We report a pre‐planned subgroup analysis of pooled Phase <jats:styled-content style="fixed-case">II</jats:styled-content> data from the <jats:styled-content style="fixed-case">AURA</jats:styled-content> Extension and <jats:styled-content style="fixed-case">AURA</jats:styled-content>2 trials to investigate the efficacy and safety of osimertinib in Japanese patients. This study included 81 Japanese patients. Patients were administered 80 mg osimertinib orally once daily until disease progression. The main endpoints were objective response rate (<jats:styled-content style="fixed-case">ORR</jats:styled-content>), <jats:styled-content style="fixed-case">PFS</jats:styled-content>, and safety. The <jats:styled-content style="fixed-case">ORR</jats:styled-content> was 63.6% and median <jats:styled-content style="fixed-case">PFS</jats:styled-content> was 13.8 mo. Overall survival rate at 36 mo was 54.0%. The most common all‐cause adverse events (AEs) were rash (grouped term; 65.4%), diarrhea (51.9%), paronychia (grouped term; 49.4%), and dry skin (grouped term; 39.5%). Most <jats:styled-content style="fixed-case">AE</jats:styled-content>s were grade 1‐2. Five patients (6.2%) developed interstitial lung disease, resulting in two deaths (2.5%). Osimertinib demonstrated favorable <jats:styled-content style="fixed-case">ORR</jats:styled-content> and <jats:styled-content style="fixed-case">PFS</jats:styled-content> in Japanese patients, similar to the overall population. Additionally, osimertinib has good efficacy and a manageable safety profile in Japanese patients with <jats:styled-content style="fixed-case">NSCLC</jats:styled-content> who had acquired resistance due to the T790M mutation.</jats:p>