Biomedical Engineering Reference
In-Depth Information
occurred in NSCLC. Laboratory research demonstrated that NSCLC
cell lines were found to overexpress the EGFR receptor compared
with small cell lung cancer (SCLC) cell lines and that there was
increasing receptor expression with advancing stage of disease.
44,45
Retrospective analyses report EGFR protein overexpression in
62% of the NSCLC, more frequently in adenocarcinomas, and that
gene copy number correlated with protein expression.
46,47
These
observations have provided the basis for evaluating
gene
amplification and protein expression as a biomarker for benefit from
anti-EGFR therapy.
EGFR
gene copy number, through either gene amplification
or high polysomy, may predict for response from EGFR TKIs.
Cappuzzo and colleagues demonstrated that patients with
A high
EGFR
EGFR
overexpression detected by fluorescence
hybridization
(FISH) had a higher objective response rate (36% vs. 3%), a superior
time to progression (9 months vs. 2.5 months) and median overall
survival (19 months vs. 7 months) with gefitinib than those who
were FISH negative.
in situ
In subset analysis of BR21, it was found that
patients who were FISH positive demonstrated a superior response
rate and an overall survival benefit with erlotinib in both univariate
and multivariate analysis.
48
33,49
The ISEL trial also demonstrated a
survival benefit for patients with a high
gene copy number with
benefits even in those with poor prognostic factors, such as smokers
and patients with non-adenocarcinoma histology.
EGFR
50
A preplanned
subgroup analysis of the INTEREST trial evaluated patients with
increased
copy number. In this selected population, gefitinib
did not demonstrate superiority to docetaxel.
EGFR
51
A study of Japanese
patients who were randomized to either gefitinib or docetaxel
reported similar conclusions with regards to increased
EGFR
copy
52
Assessing for overexpression of EGFR protein through
immunohistochemistry (IHC) has also been evaluated. Tumors
overexpressing EGFR through IHC (defined as at least 10% of cells
positive for EGFR protein expression on immunohistochemistry) was
found to correlate with response rate in the BR21 study, and survival
in patients with EGFR positive and unknown tumors in univariate
analysis.
number as INTEREST.
33
In contrast, the ISEL study found that IHC positive
patients did have a survival benefit with gefitinib compared with
IHC negative patients.
50
Erlotinib is currently indicated for patients
with advanced NSCLC with EGFR positive or unknown status and
