AMSTERDAM – While there was no overall or progression-free survival benefit, results of the randomized, controlled phase III SARAH trial showed that the use of selective internal radioactive therapy (SIRT) was better tolerated than sorafenib for the treatment of patients with advanced liver cancer.
There was also early evidence that SIRT, using the radiopharmaceutical yttrium-90 (SIR-Spheres microspheres), reduced radiologic progression in the liver and improved tumor responses to a greater extent that did sorafenib.
“I feel [the results] will open a new door in the treatment of HCC [hepatocellular carcinoma],” study investigator Valérie Vilgrain, MD, of Hôpital Beaujon, Paris, said at the International Liver Congress, sponsored by the European Association for the Study of the Liver.
Dr. Valerie Vilgrain
The standard treatment for advanced HCC at present is sorafenib, which is based on the SHARP trial findings that showed an overall survival of around 10.7 months, Dr. Vilgrain observed.
Transarterial chemoembolization (TACE) is the reference treatment for intermediate HCC, she said, and of the 467 patients included in the SARAH trial, just over 40% had failed to respond to two rounds of this therapy and had inoperable or advanced disease.
Dr. Frank Tacke, EASL vice secretary and professor of medicine in the department of gastroenterology, metabolic diseases, and intensive care medicine at University Hospital Aachen, Germany, said during a press briefing that the trial was “the first phase III, randomized controlled trial putting this intervention in perspective with current therapy.”
Dr. Tacke, who was not involved in the trial, added: “The overall survival is the same but there are so many patient-relevant parameters that are actually better in the one treatment [SIRT].”
The SARAH trial was conduced at 25 centers in France and there were 237 patients with a life expectancy of at least 3 months who were randomized to treatment with SIRT and 222 to treatment with sorafenib 800 mg daily.
The mean age of all randomized patients was 65 years, 90% were male, and 90% had cirrhosis. Cirrhosis was caused by alcoholic liver disease in 65%, hepatitis C virus infection in about one-quarter, and nonalcoholic steatohepatitis in roughly one-fifth of cases.
Comparing SIRT with sorafenib in all patients who were randomized, the median overall survival was 8.0 months versus 9.9 months (P = .018) and the median progression-free survival was a respective 4.1 months versus 3.7 months (P = .76). No differences in survival were observed when only patients who actually received the treatments were compared.
While there was no difference in radiologic progression seen overall – one of the secondary endpoints – when progression in the liver as the first site of progression was considered, there was a significant difference favoring the use of SIRT over sorafenib (P = .014), Dr. Vilgrain reported.
In addition, 26 (19%) of SIRT versus 23 (11.6%) of sorafenib-treated patients showed an objective response at 6 months, so there was “a strong signal” that SIRT could have an eventual edge over sorafenib but perhaps effects take longer to materialize (P = .042).
Fewer patients receiving SIRT than sorafenib experienced treatment-related adverse events (76.5% vs. 95%), with a median number of adverse events per patient of 5 and 10, respectively.
Adverse events of note that occurred less frequently in the SIRT than sorafenib arm were fatigue (20% vs. 41%), diarrhea (3% vs. 30%), abdominal pain (6% vs. 14%), hand-foot reaction (1% vs. 12%), infection (3% vs. 9%), weight loss (0% vs. 6%), and hypertension (0% vs. 5%).
Quality of life was significantly better in the SIRT group than in the sorafenib group over time, Dr. Vilgrain said. Quality of life was measured via the Global Health Status subscore of the EORTC QLQ-C30 scale.
Dr. Vilgrain noted during a press briefing that patients in the sorafenib group were able to start oral treatment 1 or 2 days after randomization, whereas there was a delay of 1-2 weeks before the patients randomized to SIRT could receive their treatment and just over one-quarter did not get SIRT as per the protocol, compared to 7% of those randomized to sorafenib.
Whether the lag time in patients getting their treatment might have affected the survival outcomes seen with the treatment is not known. Future studies look at reducing the time between randomization and SIRT, she said.
Dr. Vilgrain noted in an interview that SIRT was given as a single injection after an initial test injection. While it is possible to retreat patients, the study design was such that patients had to wait 6 months before they could be retreated and in theory a second treatment should not be needed.
The study was sponsored Assistance Publique – Hôpitaux de Paris (supported by grants from Sirtex Medical Limited. Dr. Vilgrain disclosed acting as a study investigator and receiving speaker fees from Guerbet and Sirtex, and speaker fees from SuperSonic Imagine and Toshiba.