Abstract 2539
Background
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.
Methods
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.
Results
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:
625PD
| 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) | ConclusionsAlthough 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 identificationNCT01774344 Legal entity responsible for the studyBayer FundingBayer DisclosureM. 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. Resources from the same session2143 - YOSEMITE: A 3 Arm Double-Blind Randomized Phase 2 Study of Gemcitabine, Paclitaxel Protein-Bound Particles for Injectable Suspension (Abraxane®) and Placebo (GAP) versus Gemcitabine, Abraxane® and either 1 or 2 Truncated Courses of Demcizumab (GAD).Presenter: Antonio Cubillo Gracian Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 2743 - A Phase 2b of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma (NCT02195180)Presenter: Pascal Hammel Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 3096 - nab-Paclitaxel (nab-P) Plus Gemcitabine (G) for Patients (Pts) With Locally Advanced Pancreatic Cancer (LAPC): Interim Efficacy and Safety Results From the Phase 2 LAPACT TrialPresenter: Philip Philip Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 1091 - A phase I and randomized phase II trial to evaluate the efficacy and safety of nab-paclitaxel (nab-P) in combination with gemcitabine (G) for the treatment of patients with ECOG 2 advanced pancreatic cancer (PDAC).Presenter: Manuel Hidalgo Session: Gastrointestinal tumours, non-colorectal Resources: Abstract Slides 5988 - New promising combination therapy of a mitochondrial metabolism inhibitor with mFOLFIRINOX in pancreatic cancerPresenter: Angela Alistar Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 5986 - Anti-CTGF human recombinant monoclonal antibody pamrevlumab increases resectability and resection rate when combined with gemcitabine/Nab-paclitaxel in the treatment of locally advanced pancreatic cancer patientsPresenter: Ewa Carrier Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 2205 - A phase III trial of muparfostat (PI-88) as adjuvant therapy in patients with hepatitis virus related hepatocellular carcinoma (HV-HCC) after resectionSession: Gastrointestinal tumours, non-colorectal Resources: Abstract 937 - A randomized phase III trial comparing 4 courses and 8 courses of S-1 adjuvant chemotherapy for p-stage II gastric cancer: JCOG1104 (OPAS-1)Presenter: Takaki Yoshikawa Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 3861 - Comparison of the eighth and seventh editions of the American Joint Committee on Cancer TNM staging systems for gastric cancer: proposal for a simplified and improved TNM staging systemPresenter: Junpeng Lin Session: Gastrointestinal tumours, non-colorectal Resources: Abstract Gastrointestinal tumours, non-colorectal: Invited Discussant 620PD, 621PD, 622PD and 623PDPresenter: Stefano Cascinu Session: Gastrointestinal tumours, non-colorectal Resources: Webcast This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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