Study IDs possible marker of EGFR
inhibitors in lung cancer patients
Patients with advanced non–small-cell lung cancer (NSCLC) whose tumor
cells contain extra copies of the epidermal growth factor receptor (EGFR)
gene may be more likely to respond to the drug gefitinib (Iressa), and this
high gene copy number may be an effective predictor of gefitinib efficacy,
according to a new study in the May 4 issue of the Journal of the National
Cancer Institute.
EGFR inhibitors have a significant effect in a sub-population of patients
with NSCLC. However, the problem that physicians face is how to select the
group of patients who will benefit.
NSCLC is the leading cause of death worldwide. In patients with advanced
disease, chemotherapy produces only modest survival benefits. However, about
12 to 27 percent of advanced NSCLC patients respond to tyrosine kinase inhibitors,
such as gefitinib and erlotinib (Tarceva). Methods to predict which patients
are most likely to respond to these drugs are under development.
To investigate possible predictive markers for gefitinib efficacy, Fred R.
Hirsch, MD, PhD, and colleagues evaluated EGFR status, gene copy number,
and protein expression and Akt activation status in 102 patients with advanced
NSCLC.
“Cancer research is leading us in a direction where we can customize cancer
therapy to treat every patient based on the biological profile of their tumor,” explained
Dr. Hirsch.
“ The results we found in this study are an example of how
useful it is for us to profile the tumor to provide therapies that the patients
are more likely to respond to.”
Amplification or high copy number of the EGFR gene (33 of 102 patients) was
associated with a better response rate (36 percent versus 3 percent), disease
control rate (67 percent versus 26 percent), time to progression (9.0 months
versus 2.5 months), and survival (18.7 months versus 7.0 months) compared
with patients with a low number of or no extra copies of the EGFR gene.
A
similar association was found for patients with high protein expression (58
of 98 patients) compared with patients with low protein expression. EGFR
mutations (15 of 89 patients) were also associated with a better response
rate and time to progression. However, further statistical analysis revealed
that only high EGFR gene copy number is associated with better survival.
“In conclusion, results from this study demonstrate that gefitinib is most
effective in advanced NSCLC patients with high EGFR gene copy number, expression,
or EGFR mutations. Because only high EGFR gene copy number was associated
with prolonged survival… and because [fluorescence in situ hybridization
(FISH)] is a readily available clinical test, the EGFR FISH analysis represents
an ideal test for selecting candidate NSCLC patients for gefitinib therapy,” the
authors write.
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