Abstract 5562
Background
Selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres was compared to sorafenib 400mg bid in a phase 3 randomised trial (SARAH) in the treatment of intermediate or advanced hepatocellular carcinoma (HCC) not amenable to curative treatment. The trial did not show a survival benefit of SIRT over sorafenib in the intention to treat (ITT) population. The effectiveness of SIRT may depend on the tumour-absorbed dose, which can be predicted with the analysis of SPECT/CT imaging during each patient work-up, before the administration of SIRT. In this post hoc analysis we explored the comparative effectiveness of SIRT and sorafenib in a subgroup of patients defined by their predicted tumour-absorbed dose.
Methods
Cox proportional hazards regressions were conducted in the ITT population of the SARAH trial. Since predicted tumour-absorbed dose was only available for SIRT, the comparisons between SIRT at a given dose and sorafenib were not randomised. Inverse probability of treatment weighting (IPTW) using propensity scores was used to account for potential confounding by differences in prognostic factors between the treatment arms, with the sorafenib sample reweighted to match the SIRT patients. A cut-off value of 100 Gy was used for tumour absorbed dose, approximating the median dose, with 120 Gy used in a sensitivity analysis.
Results
For patients with a predicted dose ≥100 Gy, the hazard ratio (HR) for overall survival (OS) from the unweighted sample was 0.70 (95% CI: 0.50-0.98, p = 0.04). After reweighting, the HR was 0.74 (95% CI: 0.51-1.04, p = 0.09). Predicted mean OS was 22.5 months (mos) for SIRT vs 17.9 mos for sorafenib. Results were similar with a 120 Gy cut-off: the HR for OS was 0.76 (95% CI 0.52-1.10, p = 0.14). Among patients who received subsequent curative therapy post-SIRT, 11/12 were alive at the end of follow-up (median 26.6 mos, range 16.0-34.8) and only one had a predicted dose <100 Gy.
Conclusions
The analysis suggests that HCC patients may derive a meaningful benefit from treatment using SIRT with a predicted dose ≥100 Gy compared to sorafenib. This may inform personalised treatment selection and clinical trial design.
Clinical trial identification
NCT01482442.
Editorial acknowledgement
Legal entity responsible for the study
Sirtex Medical UK Ltd.
Funding
Sirtex Medical UK Ltd.
Disclosure
N.S. Hawkins: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Sirtex. P.J. Ross: Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Roche; Honoraria (self), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): Sanofi; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sirtex. D.H. Palmer: Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca. V. Vilgrain: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sirtex. All other authors have declared no conflicts of interest.
Resources from the same session
3180 - Genomic analysis of hepatobiliary lithiasis associated cholangiocarcinoma revealed a distinct subtype feature.
Presenter: Lunda Gu
Session: Poster Display session 2
Resources:
Abstract
4891 - Comparison of the impact of stereotactic body radiation therapy vs. radiofrequency ablation on liver function in patients with single hepatocellular carcinoma: A propensity score matching analysis
Presenter: Masayuki Ueno
Session: Poster Display session 2
Resources:
Abstract
3203 - Exploratory analysis based on tumor location and early metabolic tumor response of REACHIN, a randomized double-blinded placebo-controlled phase II trial of regorafenib after failure of gemcitabine/platinum-based chemotherapy for advanced and metastatic biliary tract tumors.
Presenter: Anne Demols
Session: Poster Display session 2
Resources:
Abstract
1602 - Predictive Value of Neutrophil-Lymphocyte Ratio (NLR) And Platelet-Lymphocyte Ratio (PLR) In Hepatocellular Carcinoma (HCC) Patients Treated with Nivolumab (N)
Presenter: Sirish Dharmapuri
Session: Poster Display session 2
Resources:
Abstract
2848 - Preliminary Safety and Pharmacokinetics of a New Lysosomotropic Oral Agent, GNS561, in a First-in-Human Study in Advanced Primary Liver Cancer Patients
Presenter: Ahmad Awada
Session: Poster Display session 2
Resources:
Abstract
1396 - A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC): updated results
Presenter: Josep Llovet
Session: Poster Display session 2
Resources:
Abstract
1139 - Multicentric prospective study of validation of angiogenesis-related gene polymorphisms in HCC patients treated with sorafenib: Final results of INNOVATE study
Presenter: Andrea Casadei-gardini
Session: Poster Display session 2
Resources:
Abstract
4688 - Prognostic and predictive factors from the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (aHCC)
Presenter: Tim Meyer
Session: Poster Display session 2
Resources:
Abstract
1492 - A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL.
Presenter: David Pinato
Session: Poster Display session 2
Resources:
Abstract
3159 - Anlotinib for advanced hepatocellular carcinoma: interim results from the phase II ALTER0802 study
Presenter: AiPing Zhou
Session: Poster Display session 2
Resources:
Abstract