Does Radiation Therapy Improve Survival in Hepatocellular Carcinoma Compared with Sorafenib Alone?

Sorafenib was once standard first-line treatment for inoperable or metastatic hepatocellular cancer (HCC) but has since been replaced by combination immunotherapy or by immunotherapy combined with bevacizumab. Prior to that shift, investigators initiated an open-label, randomized, phase 3 trial to evaluate whether adding stereotactic body radiotherapy (SBRT) to first-line sorafenib improved overall survival (OS) in patients with Child-Pugh A liver function and HCC not amenable to resection, ablation, or transarterial chemoembolization.

Patients assigned to sorafenib alone received 400 mg twice daily. Those assigned to SBRT and sorafenib received SBRT dosed at 27.5 to 50 Gy in 5 fractions over 5 to 15 days, followed by sorafenib 200 mg twice daily starting 1 to 5 days after radiotherapy and then escalated to 400 mg twice daily as tolerated. Of 177 patients, 49% had clinical stage T3b disease, 74% had macrovascular invasion, 41% had hepatitis C, and 19% had hepatitis B with or without hepatitis C; the median sum of HCC diameter was 7.8 cm. Median follow-up was 13.2 months.

Median OS was 15.8 months with the addition of SBRT and 12.3 months with sorafenib alone, a difference that reached statistical significance only after multivariate adjustment (hazard ratio, 0.72; 95% CI, 0.52–0.99). Progression-free survival was improved with SBRT (median, 9.2 vs. 5.5 months; HR, 0.55; 95% CI, 0.40–0.75), as was response rate (38% vs. 9%). Grade 3/4 treatment-related adverse events occurred in 34% of patients receiving SBRT and 6% of those receiving sorafenib alone.