P1.01-77 Osimertinib in the First-Line Treatment of Non-Small Cell Lung Cancer Harboring Activating EGFR Mutation from Circulating Tumor DNA

Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for both EGFR activating and T790M resistant mutation. In this trial, the treatment efficacy of osimertinib was assessed in previously untreated patients with advanced or metastatic non-small cell lung carcinoma (NSCLC) harboring the EGFR activating mutation, which was detected from circulating tumor DNA (ctDNA) combined with tumor genotyping. Venous blood sampling was performed from the patients with EGFR activating mutation confirmed by tissue genotyping. To extract ctDNA from the plasma, 15 mL of peripheral blood was withdrawn and centrifuged, immediately before storage. CobasTM v2 and PANA MutyperTM were used for ctDNA genotyping. Patients with the EGFR activating mutation, detected from ctDNA, were enrolled and received a once-daily administration of osimertinib, 80 mg. The primary endpoint was objective response rate (ORR), and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety of osimertinib treatment (ClinicalTrials.gov, Identifier: NCT02769286). Thirty-nine patients with activating EGFR mutations in tumor genotyping were screened from February 2017, and the enrollment of the last patient was completed in March 2018. The ctDNA of 29 patients was positive for activating EGFR mutation, and 19 patients were enrolled (exon 19 deletion, n=11; L858R or L861Q, n=7; G719A, n=1). Median age was 70 years (range 32-84) and the majority of patients had brain metastasis (15/19, 78.9%). In the response-evaluable population (n=17), ORR was 64.7% (11/17) and DCR was 94.1% (16/17). According to EGFR mutation type of tumor genotyping, patients with exon 19 deletion showed more favorable ORR (8/9, 88.9%) than patients with exon 21 L858R/L861Q (3/7, 42.9%). In patients evaluable for CNS response (n=14), DCR of brain metastasis was 100.0% (14/14). The sensitivity of the ctDNA tests for activating EGFR mutation was 74.4% when using both tests, and 61.5% (Mutyper) or 64.1% (Cobas V2) with either test. Only one patient experienced drug-related interstitial pneumonia of grades ≥3 and resulted in drug discontinuation. Survival data including PFS was not matured (2/19, 10.5%) and the analysis will be followed. Osimertinib had favorable efficacy in first-line treatment of NSCLC harboring the EGFR activating mutation, detected from ctDNA combined with tumor genotyping, even though in patients with old age and brain metastasis.