growth factor receptor (EGFR) protein on their
surface. An increased level of EGFR protein found in the tumor
tissue causes the tumor to grow aggressively and to
metastasize. A number of EGFR-targeted agents
including the EGFR inhibitors gefitinib
('IRESSA®', ZD1839) and
erlotinib ('Tarceva™', OSI-774), and the monoclonal antibody cetuximab ('Erbitux',
IMC-C225) have been developed for a variety of
anti-cancer treatments.
For the non-small
cell lung cancer treatment, gefitnib,
developed and commercialized by
London,
UK-based
AstraZeneca
(NYSE ADS :AZN),
and erlotinib,
co-developed and commercialized by OSI Pharmaceuticals, Inc.
and Genentech, which is majority-owned by Switzerland's Roche Holding
AG (OTC ADR : RHHBY.PK),
work by attaching itself to the EGFR and thereby
inhibiting the attachment of the EGFR to the epidermal
growth factor (EGF).
In cell biology, an attachment of
the EGFR to the EGF activates the enzyme tyrosine kinase,
which causes the cell to grow and multiply. Hence, an
EGFR tyrosine kinase inhibitor will cause cells to stop
growing. Human epidermal growth receptor 1 (HER1), for
example, is one
of the several proteins which are found on the surface
of many tumor cells. What is the Real
Issue Concerning the EGFR
Protein Expression Status and Tarceva's Competitiveness
in the Lung Cancer Drug Market?
- Analysis of the impact of EGFR expression status,
as determined by immunohistochemistry (IHC) found in the Tarceva's package insert, based
upon 238 study patients, or one-third of the tested
population, shows that the survival of patients with the positive
EGFR expression status is greater than that with the
negative EGFR expression status. Immunohistochemistry
(IHC)
using the EGFR pharmDx™ kit from Carpinteria, Ca-based
DakoCytomation, Inc.,
is a quantitative analysis to identify the EGFR
expression in normal and neoplastic tissues. In this
analysis, specimens from the biopsy are IHC stained and
visually inspected. EGFR-negative is
defined if cells are absent from staining within the tumor.
In the Tarceva study, EGFR-positive was defined as having at least 10% of
the cells
stained, in contrast to the 1% cut-off specified in the
Dako EGFR pharmDx™ kit
instructions. According to DakoCytomation, the EGFR pharmDx™
kit is FDA-approved and is currently used to identify the
treatment
eligibility for colorectal cancer patients with Erbitux™.
Nonetheless, the use of the pharmDx™ kit has not been validated for
use in non-small cell lung cancer tissue. The
analysis for EGFR expression in cell tissues is quite
routine. Anatomic pathology laboratories such as Riviera
Beach, Fl-based AmeriPath, Inc., can run the analysis and
provide results within 24 hours from the receipt of the specimen.
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