HOUSTON-Erlotinib
(Tarceva) is active in hepatocellular
carcinoma and is well tolerated, according
to interim findings of a phase
II trial at The University of Texas M.D.
Anderson Cancer Center. The results
also suggest that higher expression of
the epidermal growth factor receptor
(EGFR) may be correlated with response
to the drug, said Melanie Thomas,
MD, an assistant professor in the
Department of GI medical oncology at
M.D. Anderson, who discussed the
findings in a poster presentation (abstract
4038).
The trial is designed to accrue 80
patients who are stratified into subgroups
according to high or low expression
of EGFR, the target of erlotinib.
With 33 of 80 patients accrued to
the current trial, 25% had reached the
primary study endpoint of progression-
free survival at 16 weeks. Median
survival was 6 months. There were two
minor responses among 22 evaluable
patients, for a response rate of 9%.
Response did not correlate with other
factors, such as age, sex, presence of
cirrhosis, etiology, or alpha fetoprotein
expression.
EGFR Expression
Survival Trend
Of the eight patients who were progression-
free at 16 weeks, six had high
EGFR expression in tumor cells and
two had low expression. While not
statistically significant, the difference
suggests that expression may be a factor.
"There did seem to be a trend
toward correlation of survival with high
EGFR expression," said Keith E. Stuart,
MD, director of hepatobiliary and
gastrointestinal oncology at Beth Israel
Deaconess Medical Center, Boston,
in discussing the study.
The drug appeared to be safe and
well tolerated. Grade 3 toxicities occurred
in about one-fourth of patientsand included abdominal pain, anemia,
increased bilirubin and AST (aspartate
aminotransferase), skin infection,
vomiting, and diarrhea. All
responding patients developed skin
rash, a common event associated with
erlotinib and other tyrosine kinase inhibitors.
In discussing this trial, Dr. Stuart
noted that it was one of many studies
seeking new approaches to liver cancer.
Hepatocellular carcinoma is oneof the most common causes of death
in the world, he said, and "survival is
uniformly miserable." Five-year survival
rates in the United States have
gone from 2% in the late 1970s to 5%
in the late 1990s. Most patients are not
eligible for resection, he added, and
systemic therapies to date have had
little impact on the disease.
Because hepatocellular carcinomas
are hypervascular tumors, treatments
targeted at proteins that control angiogenesis
are of interest. These include
drugs that target EGFR, such as
erlotinib and gefitinib (Iressa), and
those that target the vascular endothelial
growth factor, such as bevacizumab
(Avastin).
A trial of erlotinib and bevacizumab
combined to treat hepatocellular
carcinoma is being instituted at M.D.
Anderson, Dr. Thomas said, and if the
combination shows efficacy, the next
step could be to combine the two drugs
with chemotherapy.