1246P - Adjusted indirect comparison using propensity score matching of osimertinib to doublet chemotherapy in patients with EGFRm T790M NSCLC who have pro...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Non-Small Cell Lung Cancer
Presenter Frank Andersohn
Citation Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383
Authors F. Andersohn1, H. Mann2, T. Mitsudomi3, T.S.K. Mok4, J. Chih-Hsin Yang5, K. Papadakis6, C. Hoyle6
  • 1Frank Andersohn Consulting & Research Services, Berlin, Germany, Institute for Social Medicine , Epidemiology and Health Economics, Charite University Medicine, 10409 - Berlin/DE
  • 2B&i, AstraZeneca, Cambridge/GB
  • 3Department Of Surgery, Division Of Thoracic Surgery, Kinki University Faculty of Medicine, Osaka-Sayama/JP
  • 4State Key Laboratory Of South China, Hong Kong Cancer Institute, Department Of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin/HK
  • 5Department Of Oncology And Department Of Medical Research, National Taiwan University Hospital, Taipei City/TW
  • 6Global Payer Evidence And Pricing, AstraZeneca, Cambridge/GB

Abstract

Background

In the absence of randomized data comparing osimertinib to platinum-based doublet chemotherapy (PBDC) in patients (pts) with metastatic epidermal growth factor receptor (EGFRm) T790M non-small cell lung cancer (NSCLC) who have progressed after EGFR-TKI, an adjusted indirect comparison can offer a robust estimate of treatment effect. The IMPRESS study placebo arm (PBDC) (data cut-off [DCO] 2014 May) included a subgroup of pts with the T790M mutation and disease progression following response to EGFR-TKI. Pts had similar demographic and disease characteristics as those in AURA extension (NCT01802632) and AURA2 (NCT02094261) trials of osimertinib (DCO May 2015), and therefore represent a valid comparator to demonstrate differences in outcomes.

Methods

The efficacy of osimertinib relative to PBDC was assessed using an adjusted indirect comparison of two non-randomized data sets comprising pts with a confirmed T790M mutation (by tissue or plasma ctDNA respectively): AURA (N = 405) and IMPRESS placebo arm (N = 60). A propensity score (PS) approach was used to adjust for differences in baseline demographics and disease characteristics. Baseline characteristics of both groups were compared using statistical tests. The PS model included 22 variables with P 

Results

Following estimation of PS for each pt and balancing across the groups (osimertinib N = 287, PBDC N = 51) osimertinib demonstrated: A statistically significant improvement in median progression-free survival (PFS) of 9.7 months vs 5.3 months (HR 0.28, 95% CI 0.19–0.42, P 

Conclusions

In this indirect comparison, a statistically significant improvement in PFS and ORR was demonstrated for osimertinib compared to PBDC. AURA3 will provide a randomized comparison of osimertinib and PBDC.

Clinical trial identification

Legal entity responsible for the study

AstraZeneca

Funding

AstraZeneca

Disclosure

F. Andersohn: Consultancy fees from AstraZeneca. H. Mann, C. Hoyle: AstraZeneca employee and stock in AstraZeneca. T. Mitsudomi: Membership on advisory boards for AstraZeneca, Chugai, Boehringer Ingelheim, Roche and Pfizer. Corporate-sponsored research for Boehringer Ingelheim, Chugai and Pfizer. No stock ownership or other substantive relationships. T.S.K. Mok: Advisory boards: AZ, Roche, Pfizer, EliLilly, BI, MerckSerono, MSD, Janssen, Clovis, Bio Marin, GSK, Novartis, SFJ, ACEA, Vertex, Aveo&Biodesix, BMS, geneDecode, OncoGenex. Grants: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis, BMS. Stock: Sanomics. Other: PrimeOncology, Amgen, PeerVoice. J. Chih-Hsin Yang: Advisory boards: Boehringer Ingelheim, Eli Lilly, Bayer, Roche / Genentech / Chugai, AstraZeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Innopharma&Merrimack. No stock ownership, research grants or other substantive relationships. K. Papadakis: Employee of AstraZeneca. No stock ownership or other substantive relationships.