SARAH Provides Support For SIRT Use In Advanced HCC

For patients with advanced hepatocellular carcinoma, selective internal radiotherapy may offer comparable overall survival to sorafenib

medwireNews: Selective internal radiotherapy (SIRT) with yttrium-90 resin microspheres has matched the overall survival (OS) duration achieved with sorafenib among patients with locally advanced and inoperable hepatocellular carcinoma (HCC) participating in an open-label phase III trial.

The patients all had locally advanced Barcelona Clinic Liver Cancer stage C disease; a new HCC unsuitable for resection, transplantation or thermal ablation after prior receipt of curative surgery or thermoablative therapy for HCC; or had HCC previously unsuccessfully treated with two rounds of transarterial chemoembolisation.

OS was a median 8.0 months for the intention-to-treat (ITT) population of 237 patients who were randomly assigned to receive SIRT 2–5 weeks after entering the trial. This did not significantly differ from the median OS of 9.9 months for the 222 patients who were assigned to receive sorafenib 400 mg twice daily, the SARAH investigators report.

Valérie Vilgrain, from Hôpital Beaujon in Paris, France, and team say that OS was 9.9 months for both arms in per protocol analysis and that progression-free survival was also comparable between the groups in ITT analysis, at a median of 4.1 months with SIRT and 3.7 months with sorafenib.

But the researchers note in The Lancet Oncology that the cumulative incidence of disease progression within the liver as the first event was significantly reduced in the SIRT patients compared with their sorafenib-treated counterparts, whereas the reverse was true for the cumulative incidence of progression outside the liver.

“These results suggest that SIRT has local efficacy in the liver and sorafenib has systemic efficacy”, they write, adding that the rate of tumour response in the ITT population was also significantly higher with SIRT than sorafenib, at 19% versus 12%.

In addition, SIRT was associated with lower rates of total treatment-related adverse events than sorafenib (77 vs 94%) and of grade 3 or more severe treatment-related adverse events (41 vs 63%), with the latter most commonly fatigue (9 vs 19%), liver dysfunction (11 vs 13%), elevated liver enzymes (9 vs 7%) and haematological abnormalities (10 vs 14%).

This was reflected in the significantly better quality of life with SIRT, the researchers say, adding that 64% of patients discontinued sorafenib for drug-related toxicity, including 78% who permanently ended treatment.

“These results suggest that SIRT might be better tolerated than sorafenib in patients with locally advanced or intermediate-stage hepatocellular carcinoma, and these results might lead to changes in the recommended treatment algorithm for these patients”, Valérie Vilgrain et al conclude.

Writing in an accompanying comment, Ahmed Omar Kaseb, from the University of Texas MD Anderson Cancer Center in Houston, USA, says the SARAH trial “addresses an important question in the management of unresectable [HCC]” but that “various limitations prevent a definitive conclusion.”

He highlights that SIRT addressed only liver disease whereas sorafenib is a systemic therapy, writing that “it is not clear how many patients progressed in non-treated areas after the first SIRT session and if some patients developed metastatic disease (and whether they were then discontinued from the study to receive systemic therapy).”

And although the option of repeat SIRT was available on liver progression, the team did not describe any technical challenges associated with further radiation, the commentator observes.

Ahmed Omar Kaseb concludes: “[F]uture randomised clinical trials of hepatocellular carcinoma are warranted to assess the efficacy of sorafenib combined with SIRT compared with sorafenib alone in the unlimited metastatic disease setting to ascertain whether SIRT can control local liver tumours and thus offer a survival advantage.”


Vilgrain V, Pereira H, Assenat E, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol; Advance online publication 26 October 2017. DOI:

Kaseb AO. Grant, deny, or reassess the role of yttrium-90 in hepatocellular carcinoma? Lancet Oncol; Advance online publication 26 October 2017. DOI:

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