LBA1_PR - Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts

Date 14 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session New strategies for EGFR addicted NSCLC
Topics Anticancer agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter Suresh Ramalingam
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors S. Ramalingam1, J.C. Yang2, C.K. Lee3, T. Kurata4, D. Kim5, T. John6, N. Nogami7, Y. Ohe8, P.A. Jänne9
  • 1Department Of Hematology And Medical Oncology, Winship Cancer Institute of Emory University, 30322 - Atlanta/US
  • 2Department Of Oncology, National Taiwan University Hospital, Taipei/TW
  • 3Medical Oncology, St George Hospital, Kogarah/AU
  • 4Department Of Thoracic Oncology, Kansai Medical University Hirakata Hospital, Osaka/JP
  • 5Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 6Medical Oncology, Austin Health/ Olivia Newton-John Cancer Research Institute, Heidelberg/AU
  • 7Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama/JP
  • 8Department Of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa-City/JP
  • 9Lowe Center For Thoracic Oncology, Dana Farber Cancer Institute, Boston/US



Osimertinib (AZD9291) is a potent, irreversible EGFR-TKI selective for EGFR-TKI-sensitising (EGFRm) and T790M resistance mutations. We present updated efficacy and safety results from two Phase I expansion cohorts who received osimertinib 80 mg or 160 mg as first-line treatment for advanced EGFRm NSCLC in the AURA study (NCT01802632).


Treatment-naïve patients (pts) with locally advanced or metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily. The objectives were to investigate the efficacy and safety of osimertinib in a first-line setting. EGFRm status was confirmed via local testing and/or central laboratory testing (cobas® EGFR Mutation Test). Key eligibility criteria included measurable disease, a WHO performance status of 0/1 and acceptable organ function. Pts with stable asymptomatic brain metastases were eligible.


Overall, 60 pts were enrolled at two dose levels (80 mg, n = 30; 160 mg, n = 30): 75% female; 72% Asian; 40% with EGFR exon 19 deletion, 42% L858R mutation; five pts were EGFR T790M positive by central test at entry. At the 4th January 2016 data cut-off, median follow-up was 16.6 mths. The confirmed overall objective response rate (ORR) (95% CI) was 77% (64, 87). The ORR was 67% (47, 83) in the 80 mg cohort and 87% (69, 96) in the 160 mg cohort. Median duration of response was not reached (95% CI 12.5, not calculable [NC]) overall. Median progression-free survival (PFS) was 19.3 mths (95% CI 13.7, NC) overall, not yet reached in the 80 mg cohort (95% CI 12.3, NC) and 19.3 mths (95% CI 11.1, 19.3) in the 160 mg cohort. The proportion of pts progression free at 18 mths was 55% overall, 57% in the 80 mg cohort and 53% in the 160 mg cohort. The disease control rate was 97% overall (95% CI 88.5, 99.6). Dose reduction to manage adverse events (AEs) was required in 10% (3/30) and 47% (14/30) of pts at 80 mg and 160 mg, respectively. The most common AEs (% [Grade ≥3]) were diarrhoea (80 mg, 60% [0]; 160 mg, 87% [7%]), stomatitis (80 mg, 43% [0]; 160 mg, 50% [3%]) and paronychia (80 mg, 30% [0]; 160 mg, 53% [7%]).


First-line osimertinib for advanced EGFRm NSCLC results in a high ORR, promising PFS and manageable tolerability profile.

Clinical trial identification

NCT01802632 (25 February 2013)

Legal entity responsible for the study





S. Ramalingam: Consultancy fees: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Genentech, Lilly, Merck, Novartis. J.C.-H. Yang: Advisory board: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, AstraZeneca, Astellas, Bayer, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene. C.K. Lee: Advisory board AstraZeneca. T. Kurata: Honoraria: AstraZeneca, Chugai, Eli Lilly, Pfizer, Boehringer Ingelheim. Y. Ohe: Rec'd research grant: AZ, Chugai, Eli Lilly, ONO, BMS, Kyorin, Dainippon-Sumitomo, Pfizer, Taiho, Novartis, Merck Serono. Rec'd honoraria: AZ, Chugai, Lilly, ONO, BMS, Daiichi-Sankyo, Nippon­kayaku, BI, Bayer, Pfizer, MSD, Taiho, Clovis, Sanofi. P.A. Jänne: Consultancy fees: AstraZeneca, Pfizer, Roche. Research support: AstraZeneca, Astellas Pharma. Stock ownership: Gatekeeper Pharma. Other: Post marketing royalties on Dana-Farber Cancer Institute owned patent on EGFR mutations licensed to Lab Corp. All other authors have declared no conflicts of interest.