番茄社区

AMSTERDAM -- Tiny radioactive beads appeared to offer better safety and quality of life -- but not longer life -- than the standard targeted therapy for patients with liver cancer, a researcher said here.

In a randomized phase III trial pitting selective internal radiation therapy (SIRT) against sorafenib (Nexavar), there was no statistical difference in overall survival, according to Valérie Vilgrain, MD, of the Hôpital Beaujon in Clichy, France.

On the other hand, patients getting the radioactive beads had only half as many adverse events as sorafenib patients and reported better quality of life, Vilgrain said at the International Liver Congress, the annual meeting of the European Association for the Study of the Liver (EASL).

The investigator-initiated trial has the potential to change practice, commented Frank Tacke, MD, PhD, of University Hospital Aachen in Germany, who was not part of the study but who moderated an EASL media briefing.

"When I first read the abstract, I thought 'OK, it doesn't work' and that's not what you need with such an invasive procedure," Tacke told 番茄社区. But on closer reading, he said, it turns out to be a more positive study than it seemed at first sight.

"You do increase survival with sorafenib, but you are not doing worse with SIRT," he said.

And the improved side effect profile -- with fewer and milder events associated with SIRT -- could be a benefit for patients with advanced liver cancer, Tacke said.

Vilgrain's group at 25 French centers enrolled 467 patients with advanced hepatocellular carcinoma (HCC) or inoperable HCC who had failed two rounds of transarterial chemoembolization (TACE). Patients with metastases outside the liver were excluded, she said.

The patients were randomly assigned to receive sorafenib at 800 mg a day or SIRT with yttrium-90 resin microspheres (SIR-spheres). The radioactive beads are injected into liver arteries carefully chosen so that the SIR-spheres lodge in or near the tumors, Vilgrain told 番茄社区.

About 10% of patients assigned to SIRT wound up being treated with sorafenib because their condition worsened during the workup for SIRT (carefully mapping liver arteries so the beads were properly directed), which could take as long as 3 weeks, or because of technical issues with the mapping or administration of the beads.

In clinical practice, that time could probably be shortened substantially, Vilgrain noted.

The primary endpoint of the study was overall survival (OS), and on that basis both interventions were the same: among the patients who followed the study protocol, average survival was 9.9 months for both groups.

The same lack of difference was seen in the intent-to-treat population for OS, progression-free survival, and progression at any site, she said.

When the investigators looked at progression in the liver as a first event, Vilgrain's group did see a difference: Sorafenib patients were significantly more likely to have progression in the liver than those getting SIRT.

Also, tumor response by the RECIST criteria showed an edge for the radioactive beads: An objective response rate of 30% compared with 23% for sorafenib.

"We expected and we got a better response in the liver because it's a local therapy," Vilgrain said, "but the response didn't translate into better survival," adding that one possible reason may have been that the patients had very severe disease.

The adverse event profile favored SIRT, Vilgrain reported. During a median follow-up of 28 months, SIRT patients reported a total of 1,297 treatment-related events, 230 of them grade 3 or higher. In contrast, sorafenib patients reported 2,837 events, 411 of the grade 3 or higher.

Almost all of the sorafenib patients reported at least one treatment-related event, compared with three-quarters of SIRT patients. The median number of events per patient was doubled in the sorafenib arm at 10 versus five.

Finally, IRT patients felt significantly better than sorafenib patients, based on responses to the global heath subscore of the .

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