Internal Radiotherapy vs Kinase Inhibitor in Advanced Hepatocellular Carcinoma
A French phase III trial has shown no significant survival difference between selective internal radiotherapy with yttrium-90 resin microspheres vs sorafenib (Nexavar) in patients with advanced hepatocellular carcinoma. The findings were reported by Vilgrain et al in The Lancet Oncology.
Study Details
In the open-label SARAH trial, 459 eligible patients with locally advanced and inoperable disease after unsuccessful transarterial chemoembolization from 25 sites were randomized between December 2011 and March 2015 to receive selective internal radiotherapy with yttrium-90-loaded resin microspheres 2 to 5 weeks after randomization (n = 237) or sorafenib at 400 mg twice daily (n = 222). In the selective internal radiotherapy group, 53 patients (22%) did not receive selective internal radiotherapy, with 26 (49%) of these patients receiving sorafenib. The primary reasons for receiving sorafenib or no treatment rather than selective internal radiotherapy were technical reasons or worsening disease. The primary endpoint was overall survival in the intention-to-treat population.
Survival
The median follow-up was 27.9 months in the selective internal radiotherapy group and 28.1 months in the sorafenib group. The median overall survival was 8.0 months vs 9.9 months (hazard ratio [HR] = 1.15, P = .18) in the intent-to-treat analysis. In the per-protocol population, the median overall survival was 9.9 months among 174 patients in the selective internal radiotherapy group vs 9.9 months among 206 in the sorafenib group (HR = 0.99, 95% confidence interval = 0.79–1.24).
Adverse Events
Grade ≥ 3 treatment-related adverse events occurred in 41% of the selective internal radiotherapy group vs 63% of the sorafenib group, with the most common being fatigue (9% vs 19%), liver dysfunction (11% vs 13%), increased laboratory liver values (9% vs 7%), hematologic abnormalities (10% vs 14%), diarrhea (1% vs 14%), abdominal pain (3% vs 6%), increased creatinine (2% vs 6%), and hand-foot skin reaction (< 1% vs 6%). Serious adverse events occurred in 77% vs 82% of patients and were considered related to treatment in 20% vs 26%. Death considered related to treatment occurred in 19 patients in the selective internal radiotherapy group and 12 patients in the sorafenib group.
Assessment of quality of life with the European Organisation for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ-C30) indicated a better global health status subscore in the selective internal radiotherapy group (group effect P = .0048; time effect P < .0001), with the between-group difference appearing to increase with time (group-time interaction P = .0447).
The investigators concluded: “In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments.”
The study was funded by Sirtex Medical Inc.
Valérie Vilgrain, MD, of the Department of Radiology, Assistance Publique-Hôpitaux de Paris, is the corresponding author of The Lancet Oncology article.
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