Osimertinib As First-Line Treatment of EGFR Mutation–Positive Advanced Non–Small-Cell Lung Cancer

摘要: Purpose The AURA study ( ClinicalTrials.gov identifier: NCT01802632) included two cohorts of treatment-naive patients to examine clinical activity and safety osimertinib (an epidermal growth factor receptor [EGFR] -tyrosine kinase inhibitor selective for EGFR-tyrosine sensitizing [ EGFRm] EGFR T790M resistance mutations) as first-line treatment EGFR-mutated advanced non-small-cell lung cancer (NSCLC). Patients Methods Sixty with locally or metastatic EGFRm NSCLC received 80 160 mg once daily (30 per cohort). End points investigator-assessed objective response rate (ORR), progression-free survival (PFS), evaluation. Plasma samples were collected at after experienced disease progression, defined by Response Evaluation Criteria in Solid Tumors (RECIST), investigate mechanisms. Results At data cutoff (November 1, 2016), median follow-up was 19.1 months. Overall ORR 67% (95% CI, 47% 83%) the 80-mg group, 87% 69% 96%) 160-mg 77% 64% 87%) across doses. Median PFS time 22.1 months 13.7 30.2 months) 19.3 26.0 20.5 15.0 26.1 Of 38 postprogression plasma samples, 50% had no detectable circulating tumor DNA. Nine 19 putative mechanisms, including amplification MET (n = 1); KRAS MEK1, KRAS, PIK3CA mutation 1 each); C797S 2); JAK2 HER2 exon 20 insertion 1). Acquired not detected. Conclusion Osimertinib demonstrated a robust prolonged NSCLC. There evidence acquired samples.