141TiP - ASTRIS: A multicenter, real world treatment study of osimertinib in EGFR T790M positive non-small cell lung cancer (NSCLC)

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Immunotherapy
Thoracic malignancies
Non-small-cell lung cancer
Therapy
Presenter Parneet Cheema
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors P.K. Cheema1, Y. Chen2, F. de Marinis3, H.C. Freitas4, S. Kim5, A. Milner6, M. Provencio7, J. Rigas6, Y. Wu8
  • 1Sunnybrook Odette Cancer Center, Sunnybrook HSC, ON M4N 3M5 - Toronto/CA
  • 2National Yang-Ming University, Taipei/TW
  • 3Division Of Thoracic Oncology, Istituto Europeo di Oncologia, 20141 - Milano/IT
  • 4AC Camargo Cancer Center, São Paulo/BR
  • 5Asan Medical Center, Seoul/KR
  • 6AstraZeneca, Cambridge/GB
  • 7Hospital Clinic y Provincial de Barcelona, Barcelona/ES
  • 8Guangdon Lung Cancer Institute, Guangdong General Hospital, Guangzhou/CN

Abstract

Background

EGFR tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutation positive advanced NSCLC. Resistance develops due to a secondary EGFR T790M mutation in approximately 60% of cases. Osimertinib is an oral, irreversible, central-nervous system (CNS) active, EGFR-TKI selective for both EGFR-TKI sensitising and T790M resistance mutations. In a Phase III trial versus platinum-based doublet chemotherapy in patients with T790M positive NSCLC (AURA3), osimertinib provided a significantly longer progression-free survival (PFS; median 10.1 mths vs. 4.4 mths; hazard ratio 0.30; 95% CI 0.23, 0.41; p < 0.001) and higher response rates (71% vs 31%; odds ratio 5.39; p < 0.001) (Mok et al, New Engl J Med 2016). Currently, there is limited evidence of the efficacy of osimertinib outside of clinical trials.

Trial design

ASTRIS is a Phase III open-label, single-arm, multi-national, real world treatment study assessing the efficacy and safety of osimertinib in patients with advanced T790M mutation positive NSCLC, who have previously received an EGFR-TKI. Approximately 3500 patients will be enrolled across Asia, Europe and North and South America on a rolling basis. Country level enrolment is to stop within 6 months of market licence approval or national reimbursement. Key inclusion criteria are adults with locally advanced or metastatic NSCLC having a confirmed T790M mutation who received a prior EGFR-TKI and have World Health Organization performance status 0 − 2. T790M status must be confirmed by an appropriately validated test. Patients with asymptomatic CNS metastases, not requiring an increasing corticosteroid dose within 2 weeks prior to osimertinib administration, are allowed. Osimertinib 80 mg will be administered orally once daily for as long as the patient continues to receive clinical benefit, as judged by the investigator. The primary efficacy outcome is overall survival: secondary outcomes include investigator assessed response rate, PFS, and time to treatment discontinuation. Baseline demographics and disease characteristics, T790M mutation testing results and safety will also be reported.

Clinical trial identification

NCT02474355 (27 May 2015)

Legal entity responsible for the study

AstraZeneca

Funding

AstraZeneca

Disclosure

P.K. Cheema: Advisory board: Astrazeneca, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, Pfizer, Merck Research sponsors: Astrazeneca, Hoffmann La Roche, Boehringer Ingelheim. Y-M. Chen: Advisory board of AstraZeneca, Boehringer Ingelheim, Roche and Merck Sharp & Dohme. H.C. Freitas: Member of ASTRIS steering committee, a research program supported by Astra Zeneca. A. Milner: Employee of AstraZeneca, who sponsored the study. M. Provencio: Honoraria for consultancy work from MSD, Bristol-Myers Squibb, Roche and Astrazeneca. J. Rigas: Consultant, through Kelly Service, for AstraZeneca in Global Medical Affairs on osimertinib (TAGRISSO). Y-L. Wu: Speaker fees from AstraZeneca, Roche, Eli Lilly. All other authors have declared no conflicts of interest.