RT Journal Article
T1 Molecular predictors of prevention of recurrence in HCC with sorafenib as adjuvant treatment and prognostic factors in the phase 3 STORM trial.
A1 Pinyol, Roser
A1 Montal, Robert
A1 Bassaganyas, Laia
A1 Sia, Daniela
A1 Takayama, Tadatoshi
A1 Chau, Gar-Yang
A1 Mazzaferro, Vincenzo
A1 Roayaie, Sasan
A1 Lee, Han Chu
A1 Kokudo, Norihiro
A1 Zhang, Zhongyang
A1 Torrecilla, Sara
A1 Moeini, Agrin
A1 Rodriguez-Carunchio, Leonardo
A1 Gane, Edward
A1 Verslype, Chris
A1 Croitoru, Adina Emilia
A1 Cillo, Umberto
A1 de la Mata, Manuel
A1 Lupo, Luigi
A1 Strasser, Simone
A1 Park, Joong-Won
A1 Camps, Jordi
A1 Sole, Manel
A1 Thung, Swan N
A1 Villanueva, Augusto
A1 Pena, Carol
A1 Meinhardt, Gerold
A1 Bruix, Jordi
A1 Llovet, Josep M
K1 Cancer
K1 Clinical trials
K1 Hepatocellular carcinoma
K1 Molecular oncology
K1 Tumour markers
AB Sorafenib is the standard systemic therapy for advanced hepatocellular carcinoma (HCC). Survival benefits of resection/local ablation for early HCC are compromised by 70% 5-year recurrence rates. The phase 3 STORM trial comparing sorafenib with placebo as adjuvant treatment did not achieve its primary endpoint of improving recurrence-free survival (RFS). The biomarker companion study BIOSTORM aims to define (A) predictors of recurrence prevention with sorafenib and (B) prognostic factors with B level of evidence. Tumour tissue from 188 patients randomised to receive sorafenib (83) or placebo (105) in the STORM trial was collected. Analyses included gene expression profiling, targeted exome sequencing (19 known oncodrivers), immunohistochemistry (pERK, pVEGFR2, Ki67), fluorescence in situ hybridisation (VEGFA) and immunome. A gene signature capturing improved RFS in sorafenib-treated patients was generated. All 70 RFS events were recurrences, thus time to recurrence equalled RFS. Predictive and prognostic value was assessed using Cox regression models and interaction test. BIOSTORM recapitulates clinicopathological characteristics of STORM. None of the biomarkers tested (related to angiogenesis and proliferation) or previously proposed gene signatures, or mutations predicted sorafenib benefit or recurrence. A newly generated 146-gene signature identifying 30% of patients captured benefit to sorafenib in terms of RFS (p of interaction=0.04). These sorafenib RFS responders were significantly enriched in CD4+ T, B and cytolytic natural killer cells, and lacked activated adaptive immune components. Hepatocytic pERK (HR=2.41; p=0.012) and microvascular invasion (HR=2.09; p=0.017) were independent prognostic factors. In BIOSTORM, only hepatocytic pERK and microvascular invasion predicted poor RFS. No mutation, gene amplification or previously proposed gene signatures predicted sorafenib benefit. A newly generated multigene signature associated with improved RFS on sorafenib warrants further validation.
PB BMJ Group
YR 2018
FD 2018-07-16
LK http://hdl.handle.net/10668/12835
UL http://hdl.handle.net/10668/12835
LA en
NO Pinyol R, Montal R, Bassaganyas L, Sia D, Takayama T, Chau GY, et al. Molecular predictors of prevention of recurrence in HCC with sorafenib as adjuvant treatment and prognostic factors in the phase 3 STORM trial. Gut. 2019 Jun;68(6):1065-1075
DS RISalud
RD Apr 5, 2025