REG improved overall survival (OS) and time to progression (TTP) versus placebo in pts with HCC who progressed during prior sorafenib in the phase 3 RESORCE trial. This exploratory analysis evaluated potential correlations between baseline plasma protein levels and REG clinical benefit (OS and TTP) in RESORCE.
Baseline plasma samples were available from 499/573 pts. A total of 266 circulating proteins valid for analysis were quantified by a Luminex assay (Myriad RBM). The predictive and prognostic effects (HR and 95% CI) were evaluated using a Cox proportional hazards model with protein levels measured as a continuous variable. The predictive effect was modeled as a protein–treatment interaction effect and subjected to Akaike information criterion (AIC)-based selection to assess its association with OS and TTP. Subgroup analysis was done on proteins identified as significant for OS and TTP to generate a patient-wise protein composite score.
The overall and biomarker cohorts were similar for demographic variables and outcomes. Five proteins were predictive for OS (Table), but were not prognostic; 47 were predictive for TTP (6 were prognostic) and included the 5 proteins predictive for OS. In general, the REG treatment benefit for OS was maintained in dichotomized, quartile, and STEPP subgroup analyses, with lower protein levels correlating with improved treatment benefit. However, composite scores integrating information across predictive proteins indicated that in a small group of pts (n = 20 OS; n = 8 TTP) a high protein concentration was associated with a reduced treatment effect.Table:
|Protein||REG-predictive effect on OS, HR (95% CI)||Interaction P-value||Adjusted interaction P-value||Reference|
|LOX-1||1.35 (1.16, 1.57)|
Although this exploratory analysis suggests that most pts with HCC derive benefit from REG treatment, multiple proteins were identified as potentially predictive for OS and TTP treatment benefit with REG. Further analyses including biochemical and clinical factors are warranted.
Clinical trial identification
Legal entity responsible for the study
M. Teufel: Employment & Stock Ownership: Bayer. K. Köchert: Employment: Bayer. G. Meinhardt: Employment and Stock Ownership: Bayer. R.S. Finn: Consulting and Advisory Role: Bayer, Pfizer, Novartis, BMS, Eisai. J.M. Llovet: Research/Education Grant: Bayer, Blueprint Medicines, BI, Incyte Advisory Board: Bayer, Eisai, BMS, Eli Lilly. Consulting: Eli Lilly, Bayer, BMS, Blueprint Medicines, Eisai, Celsion, BI. J. Bruix: Research/Education Grant: Daiichi Sankyo, ArQule, Bayer, Sirtex. Honoraria: Gilead, AbbVie, Kowa, Bayer, BTG, ArQule, Terumo, Sirtex, BMS, Eisai, BI, Novartis, OSI, Roche, Onxeo. Advisory Board: Bayer, Kowa, BTG, ArQule, Terumo, Sirtex, BMS, Eisai, Novartis, OSI, Roche, Onxeo. Consulting: Gilead, AbbVie, Kowa, Bayer, BTG, ArQule, Terumo, Sirtex, BMS, BI, Kowa, Novartis, OSI, Roche, Onxeo, Daiichi Sankyo, Abbot, Glaxo, Eli Lilly.