Compared with sorafenib (Nexavar) alone, sorafenib in combination with selective internal radiation therapy did not provide a significant survival improvement for patients with advanced hepatocellular carcinoma, according to results from the palliative cohort of the SORAMIC trial presented at the 2018 World Congress on Gastrointestinal Cancer in Barcelona, Spain. However, overall survival improvements were seen with the combination in select subgroup analyses.
Jens Ricke, MD
Compared with sorafenib (Nexavar) alone, sorafenib in combination with selective internal radiation therapy (SIRT) did not provide a significant survival improvement for patients with advanced hepatocellular carcinoma (HCC), according to results from the palliative cohort of the SORAMIC trial presented at the 2018 World Congress on Gastrointestinal Cancer in Barcelona, Spain. However, overall survival (OS) improvements were seen with the combination in select subgroup analyses.
“The addition of SIRT to sorafenib treatment regimen did not result in significant improvements in survival compared with sorafenib alone,” said Jens Ricke, MD, a professor and chairman in the Department of Radiology at University Hospital Munich in Germany. “However, the combination was safe, and the toxicity profile was similar to that of sorafenib alone.”
Ricke added that subgroup analyses led to hypothesis-generating results for added SIRT in patients with non-cirrhotic HCC, patients presenting with a non-alcoholic etiology, and in younger patients.
SORAMIC is a prospective, randomized, controlled phase II trial conducted at 38 sites across Europe and Turkey (NCT01126645). The trial was conducted in 3 parts, including a diagnostic part with Primovist-enhanced MRI or contrast-enhanced multislice CT, and patients were then assigned to either a palliative or curative treatment strategy by the local investigator. In the curative cohort, patients were treated with local radiofrequency ablation of liver lesions followed by randomization to receive either systemic therapy with sorafenib or placebo.
In the palliative cohort, 424 patients were randomized 11:10 to a target dose of 400 mg twice-daily sorafenib with or without SIRT using SIR-Spheres yttrium-90 (Y-90) resin microspheres in the intention-to-treat (ITT) population. The primary endpoint was OS in the ITT group.
Patients in the palliative treatment arm had Child Pugh class A through B7 and Barcelona Clinic Liver Cancer (BCLC) stage B and C disease. Prior external beam radiation to the liver or prior treatment with monoclonal antibodies was not allowed in the study. Patients with extrahepatic disease, other than pulmonary metastases, and those who had received prior resection or local/locoregional procedures were permitted as well.
Baseline characteristics were well balanced between the 2 arms of the palliative cohort. The median age was 66 years and a majority (86%) were men. Eighty percent of the patients had cirrhosis and 25% had hepatitis C virus. Most of the patients had Child-Pugh class A disease (91%), and BCLC stage C disease (68%). Almost one-quarter of the patients (23.8%) had received prior transarterial chemoembolization.
A safety population was indicated for patients who required deviations from the standard protocol for treatment, and a per-protocol group was studied for those who did not need deviations.
The median OS with the combination was 12.1 months (95% CI, 10.6-14.6) compared with 11.5 months (95% CI, 9.8-13.9) with sorafenib monotherapy in the intent-to-treat (ITT) population (HR, 1.067; 95% CI, 0.82-1.25;P= .951).
In the per-protocol population, the median OS was 14.1 months (95% CI, 10.95-16.40) with the combination (n = 114) versus 11.1 months (95% CI, 9.7-13.9) with sorafenib alone (n = 174), although this was not found to be statistically significant (HR, 0.86; 95% CI, 0.67-1.11;P= .25).
Subgroup analyses demonstrated favor for SIRT in combination with sorafenib over sorafenib alone for patients age ≤65 (HR, 0.65; 95% CI, 0.43-1.00;P= .05), without cirrhosis (HR, 0.46; 95% CI, 0.25-0.86;P= .02), and no alcohol etiology (HR, 0.63; 95% CI, 0.45-0.89;P= .012).
Patients with liver-dominant disease, on the other hand, demonstrated favor for treatment with sorafenib alone (HR, 2.32;P= .47).
In the safety population, patients in the combination arm (n = 159) had a median of 205 days on sorafenib and a median daily dose of 485.4 mg compared with 135 days and 533.5 mg in the sorafenib monotherapy arm (n = 197). Additionally, Y-90 activity in the combination arm was seen at a median of 1.3 GBq.
Grade ≥3 adverse events were observed in 72.3% of patients in the combination arm and 68.5% of patients in the sorafenib arm from the safety population.
Ricke J, Sangro B, Amthauer H, et al. The impact of combining Selective Internal Radiation Therapy (SIRT) with sorafenib on overall survival in patients with advanced hepatocellular carcinoma: The SORAMIC trial palliative cohort. Presented at: 2018 World Congress on Gastrointestinal Cancer; June 20-23, 2018; Barcelona, Spain. Abstract O-029.