4338 - Selection of patients with hepatocellular carcinoma for selective internal radiation therapy based on tumour burden and liver function: a post-hoc analysis of the SARAH trial

Background

The most recent ESMO (2018) and EASL Clinical Practice Guidelines (2018) for the treatment of hepatocellular carcinoma (HCC) recommend considering liver function and tumour burden when selecting patients for intra-arterial therapy, such as selective internal radiation therapy (SIRT). The SARAH randomised trial did not show a statistically significant benefit of SIRT using yttrium-90 (Y-90) resin microspheres over sorafenib 400mg bid in terms of overall survival (OS) in the overall trial population of European patients with HCC. In this post-hoc analsis we explored the comparative effectivenes of these treatments in a subgroup of patients with low tumour burden (≤25% of total liver volume) and good liver function (ALBI grade 1).

Methods

A Cox proportional hazards survival regression was conducted in the intention to treat (ITT) population of the SARAH trial to explore treatment effect modification including low tumour burden/good liver function as an interaction effect with treatment.

Results

Among the ITT population, 37 (16%) patients in the SIRT arm and 48 (22%) patients in the sorafenib arm had a tumour burden ≤25% and an ALBI grade of 1. The interaction effect estimate from the Cox regression was 0.609 (95% CI: 0.344 to 1.079, p = 0.089) indicating that SIRT was relatively more effective in this subgroup. In the low tumour burden/good liver function subgroup the HR for SIRT vs sorafenib was 0.73 (95% CI: 0.44 to 1.21). Median OS was 21.9 months (95% CI: 15.2 to 32.5) for SIRT vs 17.0 months (95% CI: 11.6 to 20.8) for sorafenib. Subsequent curative therapy was more frequent after SIRT than sorafenib (14% vs 2%). The drop-out rate from randomisation to SIRT treatment was lower in the subgroup than in the overall ITT population (8% vs 22%).

Conclusions

The analysis suggests that it may be possible to select patients with HCC and a low tumour burden/good liver function, who would derive a meaningful benefit from treatment with SIRT compared to sorafenib. Further prospective validation is required.

Clinical trial identification

NCT01482442.

Editorial acknowledgement

Legal entity responsible for the study

Sirtex Medical UK Ltd.

Funding

Sirtex Medical UK Ltd.

Disclosure

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; Honoraria (self), Travel / Accommodation / Expenses: Sirtex. N.S. Hawkins: Research grant / Funding (institution), Travel / Accommodation / Expenses: Sirtex. V. Vilgrain: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sirtex. P.J. Ross: Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sirtex; Honoraria (self), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): Sanofi. All other authors have declared no conflicts of interest.