5562 - Overall survival of patients with hepatocellular carcinoma receiving sorafenib versus selective internal radiation therapy with predicted dosimetry in the SARAH trial

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.