Sirolimus improves survival for liver transplant patients with HCC

Last Updated: 2015-11-20

By Anne Harding

NEW YORK (Reuters Health) - Sirolimus provides an early benefit in recurrence-free and overall survival to liver transplantation patients with hepatocellular carcinoma (HCC), according to results of a multicenter phase 3 trial.

But the benefit was no longer evident five years after transplant, Dr. Edward Geissler, of University Hospital Regensburg in Regensburg, Germany, and colleagues found. They reported their findings online November 12 in Transplantation.

Liver transplant is the only potential curative treatment for many HCC patients, Dr. Geissler and his team note, but one in five patients has a recurrence or redevelopment of HCC after transplant. Most immunosuppressant drugs used to prevent rejection can also promote tumor development, they add, but mammalian target of rapamycin (mTOR) inhibitors such as sirolimus may actually inhibit tumor growth.

Evidence from small studies and retrospective data analyses has suggested a benefit for mTOR inhibitors in liver transplant patients with HCC. To investigate further, the researchers enrolled 525 liver transplant patients with HCC to receive immunosuppression with or without mTOR inhibitors four to six weeks after transplant. The researchers delayed treatment due to evidence that mTORs can cause hepatic artery thrombosis when used too soon after transplant.

Recurrence-free survival (RFS) was 64.5% in the group who did not receive an mTOR inhibitor and 70.2% for patients treated with sirolimus, which was not a statistically significant difference. However, a planned analysis of RFS done at yearly intervals found better outcomes three years after transplantation in the patients who received sirolimus. Overall survival (OS) was also similar at five years for the two groups, but yearly analyses showed better OS out to five years.

The early benefit in RFS and OS was about six months, Dr. Geissler noted in a telephone interview with Reuters Health. "That's fairly significant, because with a lot of antitumor therapies you're happy if you have a month or two prolongation in survival."

Subgroup analyses found that patients who met the Milan criteria for low risk fared best on sirolimus, as did patients 60 and younger and those who received sirolimus as monotherapy. Rates of serious adverse events were similar for the two groups.

"The people with the larger tumors did not benefit, and the patients that had smaller, more contained tumors had the most benefit from the therapy," Dr. Geissler said. "It was the opposite of what everyone thought when we went into the study."

About 100 patients were on monotherapy, he added. "There the results looked really good, but not everyone is comfortable to put patients on monotherapy because there is perhaps a higher chance that patients have a rejection. In our study we looked at that and we didn't see a statistically significant difference in the rejection rate in the patients that were on sirolimus monotherapy, but I think we need to look at that in more detail."

The next step, Dr. Geissler said, is to go back and look at the subgroup of patients who appeared to show the most benefit from sirolimus.

Pfizer partially supported this research. The authors reported no disclosures.

SOURCE: http://bit.ly/1X2NUGs

Transplantation 2015.