A Phase II Trial of Osimertinib in the First-Line Treatment of Non-Small Cell Lung Cancer(NSCLC) Harboring Activating EGFR Mutation from Circulating Tumor DNA (ctDNA) : LiquidLung-O-Cohort 1

Background: Treatment efficacy of osimertinib was assessed in previously untreated patients with advanced or metastatic NSCLC harboring EGFR activating mutation detected from ctDNA combined with tumor genotyping. Methods: CobasV2 and PANA Mutyper were used for ctDNA genotyping. Patients with EGFR activating mutation detected from ctDNA were enrolled and received once-daily administration of osimertinib (80 mg). Primary endpoint was objective response rate (ORR), and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR) and safety. Results: ctDNA of 29 patients was positive for activating EGFR mutation and 19 patients were enrolled. Median age was 70 years (range 32-84) and majority of patients had brain metastasis (15/19, 78.9%). ORR was 68.4% (13/19) and DCR was 94.7% (18/19). Patients with exon 19 deletion showed more favorable ORR than patients with exon 21 L858R/L861Q (10/11, 90.9% vs. 3/7, 42.9%, p=0.032). DCR of brain metastasis was 100.0% (15/15; CR=3). Sensitivity of ctDNA tests for activating EGFR mutation was 74.4% when using both tests and 61.5% (Mutyper) or 64.1% (CobasV2) with either tests. Only one patient experienced drug-related interstitial pneumonia of grade ≥3 and resulted in drug discontinuation. Survival data including PFS was not matured (7/19, 36.8%) and the analysis will be followed. Conclusion: Osimertinib had favorable efficacy in the first-line treatment of NSCLC harboring EGFR activating mutation detected from ctDNA combined with tumor genotyping, even though in patients with old age and brain metastasis.