Vilgrain V, et al. - Researchers performed a comparison of the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (⁹⁰Y) resin microspheres in patients with hepatocellular carcinoma. In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, the two groups were not significantly different regarding overall survival. Quality of life and tolerance might help when choosing between the two treatments.

Methods

• A multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial (SARAH) was performed at 25 centres specialising in liver diseases in France.
• Eligible patients were those who were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation.
• Researchers randomly assigned patients (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with ⁹⁰Y-loaded resin microspheres 2–5 weeks after randomisation.
• According to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion patients were stratified.
• For this study, the primary endpoint was overall survival.
• They performed analyses on the intention-to-treat population.
• In all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams, safety was assessed.

Results

• Random assignment of 467 patients was performed between Dec 5, 2011, and March 12, 2015; after eight patients withdrew consent, researchers assigned 237 to SIRT and 222 to sorafenib.
• 53 (22%) of 237 patients did not receive SIRT in the SIRT group; 26 (49%) of these 53 patients received sorafenib treatment.
• In the SIRT group, median follow-up period was 27·9 months (IQR 21·9–33·6) and in the sorafenib group was 28·1 months (20·0–35·3).
• In the SIRT group, median overall survival was 8·0 months (95% CI 6·7–9·9) in comparison to 9·9 months (8·7–11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94–1·41] for SIRT vs sorafenib; p=0·18).
• In the safety population, 174 (77%) of 226 patients reported at least one serious adverse event in the SIRT group and 176 (82%) of 216 in the sorafenib group.
• In this study, the most frequent grade 3 or worse treatment-related adverse events observed were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]).
• They observed 19 deaths in the SIRT group and 12 in the sorafenib group, deemed to be treatment related.