Radioembolisation (TARE) compared with sorafenib in hepatocellular carcinoma

SARAH (SorAfenib versus Radioembolisation in Advanced Hepatocellular carcinoma; NCT01482442; Vilgrain et al., Lancet Oncology 2017) and SIRveNIB (SIRT versus sorafenib; NCT01135056; Chow et al., JCO 2018) were both open-label, randomised phase 3 trials designed to show superiority of yttrium-90 resin-microsphere radioembolisation (TARE/SIRT) over sorafenib 800 mg/day in locally advanced, unresectable hepatocellular carcinoma, with overall survival as the primary endpoint.

SARAH randomised 467 patients (237 TARE, 222 sorafenib) across 25 French centres; median overall survival was 8.0 months with TARE versus 9.9 months with sorafenib (hazard ratio 1.15, 95% CI 0.94-1.41, p=0.18) — numerically worse, not better, with TARE, and the trial did not meet its superiority endpoint. SIRveNIB randomised 360 patients (182 TARE, 178 sorafenib) across 11 Asia-Pacific countries; median overall survival was 8.8 months with TARE versus 10.0 months with sorafenib (hazard ratio 1.1, 95% CI 0.9-1.4, p=0.36), again not meeting its superiority endpoint. In both trials tumour response rates were numerically higher with TARE, and grade 3 or worse adverse events and serious adverse events were significantly less frequent with TARE than with sorafenib (in SIRveNIB, grade ≥3 events in 27.7% versus 50.6% of treated patients).

The consistent message from both randomised trials is that TARE has not been shown to extend survival beyond sorafenib in this population, despite earlier retrospective and registry data suggesting a survival advantage for radioembolisation; the 2018 EASL practice guidelines subsequently did not recommend radioembolisation as a substitute for sorafenib in this setting. TARE's better tolerability and quality-of-life profile may still inform treatment choice for individual patients, but this is a caution against assuming imaging-guided intra-arterial radiotherapy is simply a 'better' alternative to systemic therapy on survival grounds alone.