AURA17 study of osimertinib in Asia-Pacific patients (pts) with EGFR T790M-positive advanced non-small cell lung cancer (NSCLC): Updated phase II results including overall survival (OS)

Abstract

Background: Osimertinib, a third-generation, EGFR-TKI, potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations. We report updated results from AURA17 (NCT02442349) including OS for the first time. Methods: Eligible pts with prior progression on EGFR-TKIs received osimertinib 80 mg once daily until no clinical benefit by investigator. Inclusion criteria: ≥18 years, T790M positive biopsy (defined by central cobas testing), WHO performance status (PS) 0/1. Asymptomatic, stable CNS metastases were allowed. Primary endpoint: objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR). A freeze time point of October 31, 2017 was used for RECIST endpoints; otherwise data cut-off (DCO) was March 20, 2018. Results: At DCO, 171 pts had received osimertinib, median treatment exposure 12.4 months (mo) (range 0.2-31.0). Baseline characteristics were representative of an Asia-Pacific population: median age 60 years; female 68%; Chinese 87%; WHO PS 1 85%. Efficacy results in the table. ORR was consistent across baseline characteristics. At DCO, 95 pts had died (56% maturity), with a median OS of 23.2 mo (95% CI 20.0, 26.7). Full analysis set: all patients enrolled who received ≥1 dose of treatment; Evaluable for response set: all patients who received ≥1 dose of treatment and have measurable disease at baseline by BICR. ∗Five patients were excluded from the evaluable for response set due to no measurable disease at baseline by BICR. ∗∗Duration of objective response, n = 103 RECIST freeze time point: October 31, 2017 was used for all RECIST related endpoints (ORR, DCR, PFS) BICR, blinded independent central review; CI, confidence interval; DCR, disease control rate; DoR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival Patients with any adverse event (AE): 98% (Grade ≥3, 35%). Any AE leading to discontinuation: 5%. Most common all causality AEs: diarrhea (35%; Grade ≥3, 1%) and rash grouped term (30%; Grade ≥3, 1%). There were 3 cases of interstitial lung disease (n = 2) and pneumonitis (n = 1). Conclusions: Osimertinib treatment in this population of pts with T790M-positive advanced NSCLC resulted in an ORR of 62% and a median OS of 23.2 mo. Osimertinib treatment demonstrated clinical activity, a durable response and similar safety profile to global osimertinib studies in pts with T790M-positive NSCLC. Data support using osimertinib for Asia-pacific pts with T790M-positive NSCLC post-progression on prior EGFR-TKI.