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.
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
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
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
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.