Tremelimumab Shows Promise in Patients With Liver Cancer

From Reuters Health Information > Conference News

Tremelimumab Shows Promise in Patients With Liver Cancer
By Fran Lowry

NEW YORK (Reuters Health) Apr 11 - Tremelimumab looked "promising" in a small phase II trial in patients with advanced hepatocellular carcinoma and hepatitis C, in some cases producing stable disease for more than a year, researchers said in Chicago earlier this month at the American Association for Cancer Research (AACR) Annual Meeting 2012.

Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes, resulting in inhibition of B7-CTLA-4 mediated downregulation of T-cell activation, explained Dr. Ignacio Melero, from El Centro de Investigacion Medica Aplicada, Universidad de Navarra, in Pamplona, Spain.

"We had data that lymphocytes in liver infiltrates of hepatocellular carcinoma and chronic hepatitis C virus-infected patients expressed CTLA-4, which is the target of this monoclonal antibody," Dr. Melero told Reuters Health.

"In addition, there was previous experience in the potential immunogenicity of hepatocellular carcinoma cells. The most exciting point for us was that we could explore the effects on a tumor target and on a viral target at the same time," he said.

Dr. Melero and his group evaluated 20 patients who received tremelimumab, 15 mg/kg IV every 90 days for a median of two cycles (range, one to four). The median age was 68; 71% of the patients were male.

Two patients had a partial response, and 11 had stable disease. The duration of stable disease was more than 12 months in 33% of patients.

On intent-to-treat analysis, the median overall survival was 7.5 months and time to progression was 6.4 months, the researchers said in an April 2nd presentation at the conference.

Dr. Melero said the treatment was "globally very well tolerated." Eighty percent of the patients had drug-related adverse events, most frequently mild to moderate rash (40%), itching (45%), increased transaminase levels (30%), fatigue (20%) diarrhea (10%) constipation (10%) and anorexia (10%). No life-threatening adverse events occurred.

The researchers also observed a reduction of hepatitis C virus in patients' blood, and this was accompanied with enhanced antiviral immunity. The median values went from 3.78 x 10e5 copies/ml at baseline, to 3.02 x 10e4 copies/ml on day 120 (p=0.02), to 1.69 x 10e3 copies/ml on day 210 (p=0.04).

These decreases in viral load were associated with an increase in anti-hepatitis C virus immune response in 76% of the patients.

Dr. Melero said tremelimumab might also have potential for use in patients with chronic hepatitis C infection. There are hopes that it might prevent or delay the development of liver cancer.

"It is clear that treating hepatitis C virus in a patient with liver cancer is nonsense because the virus has already done its worst, but there is potential to complement therapies for HCV with anti-CTLA-4 monoclonal antibodies," he told Reuters Health.

Dr. Ruth He, from Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, said it was still too early to make a definite conclusion from this small study. But, she told Reuters Health, "the compound should move forward for further evaluation. It is a unique compound because it deals with tumor immune tolerance. It's a totally new type of treatment."

The study was supported by Pfizer, and tremelimumab has been licensed by MedImmune.