ILC 2017: Selective Internal Radiation Therapy vs Sorafenib in Hepatocellular Carcinoma
Results of the SARAH trial presented at the 2017 International Liver Congress (ILC) demonstrated that selective internal radiation therapy (SIRT) resulted in a median overall survival of 8.0 months compared to 9.9 months with sorafenib (Nexavar; P = .179) in patients with locally advanced and inoperable hepatocellular carcinoma. The trial further demonstrated that the cumulative incidence of radiologic progression in the liver as the first event was significantly lower in the SIRT group compared to the sorafenib group (P = .014), and the response rate was significantly higher in the SIRT group compared to the sorafenib group (19.0% vs 11.6%, P = .042). Both the side-effect profile and quality-of-life scores were significantly better over time in the SIRT group compared to the sorafenib group (P = .005).
The prognosis for patients with advanced liver cancer is poor, and the multikinase inhibitor sorafenib is the only approved first-line systemic treatment. If patients are not tolerant or have contraindications for sorafenib therapy, there is currently no standard of care, and patients lack effective treatment options. SIRT with yttrium-90 (Y-90) resin microspheres has shown promising antitumor results with a safe profile. Further trials are needed to establish this treatment as a viable option for patients.
“Patients with advanced or inoperable hepatocellular carcinoma have a poor prognosis, often with underlying cirrhosis, and the treatment option currently available, sorafenib, has a high level of toxicity. As cohort studies have demonstrated the efficacy of SIRT with Y-90 resin microspheres, we set out to compare the efficacy of this treatment vs the current standard of care,” said Valérie Vilgrain, MD, PhD, of Hôpital Beaujon Service de Radiologie, Paris, and lead author of the study. “While SIRT demonstrated significantly reduced side effects, better quality of life, higher response rates, and more effectively controlled tumor progression in the liver, the overall survival of patients was not higher than in the sorafenib group. Nonetheless, this study provides evidence that SIRT may be a better-tolerated alternative for managing this complex and difficult-to-treat disease, deserving further evaluation.”
Study Findings
The SARAH trial was a randomized, controlled, open-label, multicenter, investigator-initiated phase III trial. Patients with locally advanced or inoperable hepatocellular carcinoma who did not respond to other treatments or had two failed rounds of transarterial chemoembolization were randomized to SIRT with Y-90 resin microspheres or oral sorafenib at 400 mg twice daily. The primary endpoint of the study was overall survival; secondary endpoints included progression-free survival, time to radiologic progression at any site and in the liver as the first event, tumor response, quality of life, safety, and toxicity.
There were 459 patients from 25 French clinical centers included in the study, 237 of whom received SIRT. The median progression-free survival was 4.1 months and 3.7 months in the SIRT and sorafenib groups, respectively (P = .765). The cumulative incidence of radiologic progression at any site did not differ in either group (P = .256).
Overall, there were 1,297 and 2,837 treatment-related adverse events, including 230 and 411 of grade ≥3, in the SIRT and sorafenib groups, respectively. The number of patients with at least 1 treatment-related adverse event was 173 (76.5%) and 203 (94.0%), (P < .001), including 92 (40.7%) and 136 (63.0%) grade ≥3 adverse events, (P < .001), in the SIRT and sorafenib groups, respectively.
Quality of life assessed using the Global Health Status scale of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire–Core 30 (EORTC QLQ-C30)—was significantly better in patients who received SIRT compared to the sorafenib group (P = .005), an advantage that tended to increase with time (P = .045).
“The SARAH trial is the first reported randomized controlled trial evaluating the survival benefit of SIRT in locally advanced hepatocellular carcinoma compared to sorafenib. SIRT was found to be safe, but regrettably the study failed to meet the primary endpoint, and SIRT did not show an overall survival superior to sorafenib. Further trials are needed to establish this treatment as a viable option for patients,” said Alejandro Forner, MD, PhD, BCLC group, Liver Unit, Hospital Clinic Barcelona, Spain, and EASL Governing Board Member.
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