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Liver-targeting treatment with selective internal radiation therapy more effectively controlled liver tumor progression and was better tolerated in patients with hepatocellular carcinoma, but the therapy did not improve rates of overall or progression-free survival over sorafenib.
Valérie Vilgrain, MD
Liver-targeting treatment with selective internal radiation therapy (SIRT) more effectively controlled liver tumor progression and was better tolerated in patients with hepatocellular carcinoma (HCC), but the therapy did not improve rates of overall or progression-free survival over sorafenib, according to findings presented at the 2017 International Liver Congress.
In the SARAH trial of SIRT versus sorafenib, patients with locally advanced or inoperable HCC receiving SIRT achieved tumor response rates of 19% compared with 11.6% in the sorafenib group (P = .042).
For the study’s primary endpoint, however, patients in both cohorts experienced similar median overall survival (OS) of 8.0 months with SIRT versus 9.9 months with sorafenib (P = .179). Median progression-free survival (PFS), a secondary endpoint, was 4.1 months versus 3.7 months in the SIRT and sorafenib groups, respectively (P = .765).
Valérie Vilgrain, MD, chair of the radiology department at Hôpital Beaujon in Paris, France, presented findings on behalf of the SARAH Trial Group. She explained the rationale behind the trial: “Patients with advanced or inoperable hepatocellular carcinoma, often with underlying cirrhosis, have a poor prognosis, 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 versus the current standard of care.”
SIRT comprises yttrium-90 resin microspheres injected into the tumors, delivering up to 40 times more radiation than would be possible using standard radiation therapy. Because SIRT is directly delivered to the tumor, surrounding healthy tissue is spared radiation exposure.
SARAH was an open-label, multicenter, investigator-initiated, phase III trial that enrolled 459 patients with locally advanced or inoperable HCC who did not respond to other treatments or who had 2 failed rounds of transarterial chemoembolization.
Investigators randomized 237 patients to SIRT and 222 patients to an active control consisting of the current standard, oral sorafenib at 400 mg twice daily.
The patients were enrolled from 25 French clinical centers, had a mean age of 65.2 years, and the majority (90.2%) were male. Advanced HCC was diagnosed in 223 patients, and the most frequent liver comorbidity was alcoholic cirrhosis in 65.1% of patients. Chemoembolization failure had occurred in 113 patients, 35 patients were not eligible for any curative treatment, and 88 patients were in both categories.
In addition to PFS and tumor response, other secondary endpoints included time to radiologic progression at any site and in the liver as the first event, quality of life, and serious adverse events (AEs).
Cumulative incidence of radiologic progression in the liver as the first event was significantly lower in the SIRT group compared with the sorafenib group (P = .014) and corresponded to a 27% reduction of the subdistribution hazard ratio ([SHR], 0.731; 95% CI, 0.569-0.939).
The cumulative incidence of radiologic progression at any site was similar in both groups (P = .256). Both the side-effect profile and quality-of-life scores were significantly better in the SIRT group compared with the sorafenib group (P = .005).
Overall, 1297 versus 2837 treatment-related AEs (TRAEs) were reported, including 230 versus 411 grade ≥3 events, with SIRT versus sorafenib, respectively. Approximately 76% of patients (n = 173) in the SIRT cohort experienced a TRAE compared with 203 patients (94%) with sorafenib (P < .001). A total of 92 (40.7%) versus 136 (63.0%) patients in the respective groups experienced grade ≥3 TRAEs (P < .001).
Quality of life, as assessed using the Global Health Status scale of the EORTC QLQ-C30 questionnaire, was significantly better in SIRT patients compared with patients receiving sorafenib (P = .005); this advantage tended to increase with time (P = .045). “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,” Vilgrain said.
SARAH represented the first head-to-head comparison of SIRT to the standard of care, but the trial did not meet its primary OS endpoint, indicating a need for additional trials to establish SIRT as a viable option for patients.
“Nonetheless, this study provides evidence that SIRT may be a better-tolerated alternative for managing this complex and difficult-to-treat disease, which deserves further evaluation,” Vilgrain concluded.
Vilgrain V, Bouattour M, Sibert A, et al. SARAH: a randomised controlled trial comparing efficacy and safety of selective internal radiation therapy (with yttrium-90 microspheres) and sorafenib in patients with locally advanced hepatocellular carcinoma. Presented at: 2017 International Liver Congress; April 19-23, 2017; Amsterdam, Netherlands. Abstract GS-012.