SARAH, a large French study of patients with advanced, inoperable hepatocellular carcinoma (HCC) has completed patient enrolment, exceeding its 400-patient target, according to its principal investigator, Valérie Vilgrain, department of radiology, Beaujon Hospital, Assistance Publique–Hôpitaux de Paris (AP-HP) and Université Paris Diderot, Sorbonne Paris Cité, France.
SARAH (sorafenib versus radioembolization in advanced hepatocellular carcinoma) is a phase III multi-centre randomised controlled study, sponsored by the AP-HP, directly compares the efficacy of selective internal radiation therapy (SIRT, or radioembolization) using yttrium-90 (Y-90) resin microspheres (SIR-Spheres Y-90 resin microspheres; Sirtex Medical Limited) versus sorafenib (Nexavar; Bayer HealthCare), a systemic therapy that is the current standard of care for patients with inoperable advanced HCC.
“SARAH is the largest randomised study ever to compare selective internal radiation therapy—or any liver-directed therapy—against the standard-of-care systemic therapy in the treatment of primary liver cancer. The SARAH study team is delighted that enrolment is now complete, with results expected in late 2016,” Vilgrain said.
SARAH is for patients in France with advanced HCC (Barcelona clinic liver cancer stage C) with or without portal vein thrombosis and no extrahepatic spread, or whose disease has progressed or recurred after previous therapies; and who are ineligible for surgical resection, ablation or liver transplantation. The study is also comparing the quality of life of patients and other measures such as the tolerability of the treatments.
Coordinated by Vilgrain, more than 25 specialist cancer centres throughout France are involved in the study. SIR-Spheres Y-90 resin microspheres were selected for the test arm of this independent, collaborative national study. “Target enrolment was reached in around three years, which is remarkable for a single-country trial of this size in a hard-to-treat cancer with few proven therapeutic choices,” Vilgrain noted.
Sorafenib was established as the standard treatment for patients with advanced HCC following the results of the pivotal SHARP randomised controlled trial, which demonstrated an increased median overall survival from eight to 11 months compared to placebo. However, 80% of patients receiving sorafenib also experienced treatment-related adverse events.
SIRT with SIR-Spheres Y-90 resin microspheres is an approved treatment for inoperable liver tumours. It is a minimally invasive treatment that delivers high doses of high-energy beta radiation directly to the tumours via a catheter into the liver arteries that supply blood to the tumours. By using the tumours’ blood supply, the microspheres selectively target liver tumours with a dose of radiation that is up to 40 times higher than conventional radiotherapy, while sparing healthy tissue.
Interest in a randomised controlled study of SIRT using Y-90 resin microspheres in this patient population was based on a substantial number of open-label single-group studies as well as a large multi-centre European study on the long-term outcomes related to survival and safety of SIR-Spheres Y-90 resin microspheres in patients with inoperable HCC. In 13 open-label single-group studies with a total of 400 patients with advanced HCC, the combined estimation of the median overall survival after radioembolization with Y-90 microspheres was 15 months, with a range of 7–27 months.
SIR-Spheres Y-90 resin microspheres are approved for the treatment of inoperable liver tumours in Australia, the European Union (CE mark), Argentina (ANMAT), Brazil, and several countries in Asia, such as India and Singapore. SIR-Spheres Y-90 resin microspheres also have a full Pre-Market Approval from the US Food and Drug Administration and are indicated in the USA for the treatment of non-resectable metastatic liver tumours from primary colorectal cancer in combination with intra-hepatic artery chemotherapy using floxuridine.