Drug & Device Development

Vandetanib shows limited clinical activity in inoperable hepatocellular carcinoma

Last Updated: 2012-02-20 9:30:01 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Vandetanib does not improve tumor stabilization rates in patients with inoperable hepatocellular carcinoma (HCC), researchers from Taiwan report.

"In general, results of our study did not meet its primary endpoint," Dr. Ann-Lii Cheng from National Taiwan University Hospital in Taipei told Reuters Health in an email. "Since this is a small phase II study, the results were not too surprising to us. However, the study did shed some light for vandetanib's activity on advanced HCC, particularly for the 100 mg/day dosing schedule."

Dr. Cheng and colleagues evaluated the tumor stabilization rate (complete or partial response or stable disease for at least four months) in 67 patients with inoperable HCC. Nineteen received vandetanib 300 mg daily, 25 received vandetanib 100 mg daily, and 23 received placebo.

The findings appear online January 13 in the Journal of Hepatology.

Dr. Cheng explained that vandetanib is a small molecule tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR).

Previous work has shown that inhibiting those receptors has a promising effect on HCC, he added.

In the new trial, however, there were no objective tumor responses by the time of data cut-off. Tumor stabilization rates did not differ significantly between vandetanib 300 mg (5.3%), vandetanib 100 mg (16.0%), and placebo (8.7%).

There was an insignificant trend toward improved progression-free survival, with median progression-free survivals of 1.05 months with vandetanib 300 mg and 1.7 months with vandetanib 100 mg, compared with 0.95 months for placebo.

There was a similar insignificant trend toward improved median overall survival: 5.75 months for vandetanib 100 mg, 5.95 months for vandetanib 300 mg, and 4.27 months for placebo.

Adverse events (most commonly diarrhea and rash) did not differ according to randomized treatment, but dose interruptions or dose reductions due to adverse events occurred only in the vandetanib groups.

VEGF levels increased and VEGFR-2 levels decreased significantly with vandetanib, but changes in other circulating angiogenic factors were not consistent between the treatment groups.

"The results of this trial do not support the hypothesis that combining VEGFR and EGFR inhibition could provide better therapeutic efficacy in patients with HCC," the authors conclude. "It is possible that the negative results are simply due to lack of predictive biomarkers that might help find patients that would most benefit from this therapeutic approach."

Despite these findings, Dr. Cheng said, "It seems to us that the activity of vandetanib on HCC deserves further exploration, probably by trials of larger scale."

The study was sponsored by AstraZeneca, which also paid a medical writer to help with the report.

SOURCE: http://bit.ly/zXlb9T

J Hepatol 2012.