Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma

BACKGROUND:

Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of a combination of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres and sorafenib with those of sorafenib alone in patients with advanced HCC.

METHODS:

SORAMIC is a randomised controlled trial comprising diagnostic, local ablation and palliative cohorts. Based on diagnostic study results patients were assigned to local ablation or palliative cohorts. In the palliative cohort, patients not eligible for TACE were randomised 11:10 to SIRT plus sorafenib (SIRT+sorafenib) or sorafenib alone. The primary endpoint was overall survival (OS; Kaplan-Meier analysis) in the intention-to-treat (ITT) population.

RESULTS:

In the ITT cohort, 216 patients were randomised to SIRT+sorafenib and 208 to sorafenib alone. Median OS was 12∙1 months in the SIRT+sorafenib arm, and 11∙4months in the sorafenib arm (hazard ratio [HR], 1∙01; 95% CI 0∙81-1∙25; p=0∙9529). Median OS in the per-protocol population, was 14∙0 months in the SIRT+sorafenib arm (n=114), and 11∙1months in the sorafenib arm (n=174; HR, 0∙86; p=0∙2515). Subgroup analyses of the PP population indicated a survival benefit of SIRT+sorafenib for patients without cirrhosis (HR, 0∙46, 0∙25-0∙86; p=0∙02); cirrhosis of non-alcoholic aetiology (HR, 0∙63, p=0∙012); or patients ≤65 years (HR, 0∙65, p=0∙05). Adverse events (AEs) of Common Terminology Criteria for AE Grades 3-4 were reported in 103/159 (64∙8%) patients who received SIRT+sorafenib, 106/197 (53∙8%) patients who received sorafenib only (p=0∙04), and 8/24 (33∙3%) patients who only received SIRT.

CONCLUSION:

Addition of SIRT to sorafenib did not result in a significant improvement in OS compared with sorafenib alone. Subgroup analyses led to hypothesis-generating results supporting future study design. Funding Financial support by Sirtex Medical and Bayer Healthcare Lay summary Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC).

In selective internal radiotherapy therapy (SIRT), also known as radioembolisation, microscopic, radioactive resin or glass spheres are introduced into the blood vessels that feed the tumours in the liver. This study found that the addition of SIRT with 90yttrium-loaded resin microspheres to sorafenib treatment in people with advanced HCC did not significantly improve overall survival compared with sorafenib treatment alone. However, the results suggest how future studies on this combination therapy in people with advanced HCC could be designed.

CITATION  J Hepatol. 2019 Aug 14. pii: S0168-8278(19)30472-6. doi: 10.1016/j.jhep.2019.08.006