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)
Authors: C. Zhou, M. Wang, Y. Cheng, Y. Chen, Y. Zhao, Y.-K. Shi, M.-J. Ahn, Y. Lu, M. Shi, J.-Y. Han, S.-W. Kim, H.-L. Zhang, G. Chen, H. Li, J. Wang, Y.-L. Wu
Journal: Annals of Oncology (2018)

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 20.0Table511P AURA17 efficacy resultsEndpoint*Evaluable for response set (n = 166)ORR,% (95% CI)62 (54, 69)DCR,% (95% CI)88 (82, 92)Median DoR, months** (95% CI)9.9 (8.3, 12.9)Full analysis set (n = 171)Median PFS, months (95% CI) Median OS, months (95% CI) Deaths, n (%)9.7 (7.0, 11.1) 23.2 (20.0, 26.7) 95 (56)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 Open table in a new tab , 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. Editorial acknowledgement: Laura Crocker. Clinical trial identification: NCT02442349. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: C. Zhou: Honoraria: Eli Lilly, Roche, Pfizer, Boehringer Ingelheim, AstraZeneca, Hengrui, Sanofi. M-J. Ahn: Speakers’ bureau: AstraZeneca, MSD, Ono, Lilly, Roche. Y. Lu: Consulting or advisory role: AstraZeneca, Eli Lilly, Roche and Pfizer. Research funding: AstraZeneca. J-Y. Han: Honoraria: Roche; Consulting, advisory role: Novartis, BMS, MSD; Research funding: Roche. G. Chen: Employee, shareholder: AstraZeneca. H. Li, J. Wang: Employee: AstraZeneca. Y-L. Wu: Honoraria: AstraZeneca, Lilly, Roche, Pfizer, Sanofi, Boehringer Ingelheim; Consulting, advisory role: AstraZeneca, Roche, Merck, Boehringer Ingelheim; Research funding: Boehringer Ingelheim, Roche. All other authors have declared no conflicts of interest.