MO29-2 Osimertinib for RT-naïve CNS metastasis of EGFRm NSCLC: pll OCEAN study (LOGIK 1603/WJOG 9116L), part of T790M cohort

∼30% of pts with EGFRm have central nervous system (CNS) metastasis. Although radiotherapy (RT) is a standard treatment, the efficacy is poor. The aim was to assess osimertinib for pts with RT-naïve CNS metastasis of EGFRm NSCLC. OCEAN study was two-cohort trial, 66 pts (T790M cohort; 40 and 1st-line cohort; 26) with RT-naïve CNS metastasis was included. The primary endpoint was the response rate of brain metastasis (BMRR) by the PAREXEL criteria. We set a threshold RR 50% and an expected RR 70% inT790M cohort (1st line cohort, 55%, 80%). Based on alpha 0.05 (one-sided) and 80% power, the sample size of T790M cohort was 40 (1st line,25). Key secondary endpoints were PFS, and ORR, BMRR by the RECIST. In this report, we present the results of T790M cohort and exploratorily assessment of the blood and CSF concentration. Between October 2016 to July 2019, 40 pts were enrolled in the T790M cohort. The median age was 66.5 with 30.0% male. Eight patients had symptomatic CNS metastasis and most pts had multiple CNS metastasis (77.5%). BMRR by PAREXEL criteria was 66.7% (95%CI, 54.3-79.1%). mPFS was 7.1m (95%CI, 3.4-13.6 m) and ORR was 40.5% (95%CI, 24.7-57.9%). Treatment related pneumonitis was observed in 4 (10.0%). There was no G3 or higher toxicities found in more than 10%. Mean plasma and CSF concentrations of osimertinib and its metabolites, AZ5104 were similar to previous reports (plasma 576 nM, 66.5 nM, CSF 4.1 nM, 0.26 nM, respectively), and the CSF to plasma ratio for osimertinib was approximately 1%. The plasma trough concentration was not correlated with the efficacy of osimertinib for CNS metastasis. This first study assessed the efficacy of osimertinib for pts with RT-naïve CNS metastasis of T790M positive NSCLC. This study met primary endpoint, and the results suggested that pts with CNS metastasis with T790M had better to receive osimertinib prior to brain RT. Clinical trial information: jRCTs071180017.