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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

2604 - Analysis of single-nucleotide polymorphisms (SNPs) in the phase 3 RESORCE trial of regorafenib versus placebo in patients with hepatocellular carcinoma (HCC)

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Translational Research

Tumour Site

Hepatobiliary Cancers

Presenters

Karl Köchert

Citation

Annals of Oncology (2018) 29 (suppl_8): viii205-viii270. 10.1093/annonc/mdy282

Authors

K. Köchert1, G. Meinhardt2, J. Bruix3, M. Teufel4

Author affiliations

  • 1 Clinical Statistics Eu – Sbu Oncology, Bayer AG, 13353 - Berlin/DE
  • 2 Clinical Development Oncology, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 3 Bclc Group, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona/ES
  • 4 Translational Medicine Oncology, Bayer HealthCare Pharmaceuticals, Whippany/US
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Resources

Abstract 2604

Background

Regorafenib is a multikinase inhibitor that improved overall survival (OS) and time to progression (TTP) in patients with HCC who progressed during sorafenib treatment in the phase 3 RESORCE trial. This exploratory analysis evaluated the impact of SNPs on regorafenib treatment benefit (OS and TTP) and the occurrence of hand–foot skin reaction (HFSR) in the RESORCE trial.

Methods

Genotyping of 187 SNPs was performed on whole blood DNA from 330/573 (58%) patients from RESORCE using a custom NimbleGen™ kit and sequencing libraries that were made using NimbleGen™ KAPA Hyper construction kits. The prognostic and predictive effects of the SNPs, as well as the impact on the occurrence of grade ≥1 HFSR, were assessed using Cox proportional hazards regression with Breslow tie handling or logistic regression, respectively. Models were adjusted for clinical covariates as determined by Akaike information criterion (AIC)-based selection and adjusted for population stratification. P values were corrected for multiple testing using Bonferroni correction and deemed significant at an adjusted α ≤ 0.05.

Results

The overall RESORCE and biomarker cohorts were generally similar for demographic variables (except the latter had a smaller proportion of Asian patients) and outcomes. None of the assessed SNPs were prognostic or predictive of OS. In contrast, 6 SNPs (positioned in the UGT1A1, VEGFC, and TIE2 genes) were prognostic for TTP; SNP rs4148323 in the UGT1A1 gene was predictive for TTP (HR 0.24, 95% CI 0.12–0.49; adjusted p = 0.012). The rs1547651 SNP in the VEGFA gene showed a significant prognostic effect on the occurrence of grade ≥1 HFSR (odds ratio [OR] 0.04, 95% CI 0.01–0.19; adjusted p = 0.037), while the rs114681547 SNP, also in the VEGFA gene, showed a predictive effect (OR 26.23, 95% CI 5.39–197.96; adjusted p = 0.038).

Conclusions

These exploratory results suggest that the detected SNP biomarkers may be candidates for future research to gain deeper understanding of the biological mechanisms determining clinical benefit of regorafenib treatment in HCC.

Clinical trial identification

NCT01774344.

Legal entity responsible for the study

Bayer.

Funding

Bayer.

Editorial Acknowledgement

Editorial assistance in the preparation of this abstract was provided by Katrin Gudmundsdottir of SuccinctChoice Medical Communications (London, UK), with financial support from Bayer.

Disclosure

K. Köchert, G. Meinhardt, M. Teufel: Stock ownership, Employee: Bayer. J. Bruix: Grants, Research support: Bayer; Advisory board: Bayer, AbbVie, Bristol-Myers Squibb, Novartis, Roche, Onxeo, Terumo, Sirtex and BTG; Consulting: Daiichi Sankyo, ArQule, Bayer, AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Kowa, Novartis, Roche, Onxeo, Terumo, Sirtex.

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