Biomedical Engineering Reference
In-Depth Information
Despite the positive findings across trials in the first, second,
and third-line setting, it was evident that the survival benefit from
these agents in unselected populations was modest (see Table 6.1);
however, it was also apparent that some patients enjoyed a rapid
and long-lasting response. As a result, efforts were initiated to
identify predictive biomarkers for the EGFR-directed agents. The
markers most consistently associated with benefit are mutations
in
EGFR
. Additional markers that have been evaluated include
EGFR
gene copy number, receptor and ligand expression and mutations
in downstream components such as the
gene. A summary of
the known biomarkers in NSCLC and their methods of detection are
presented in Tables 6.2 and 6.3, respectively.
RAS
Table 6.2
Evidence from clinical trials for predictive and prognostic
factors in NSCLC
Predictive
for anti-
EGFR
MoAbs
Predictive for
EGFR TKIs
Predictive
for toxicity
Biomarker
Prognostic
Activating
EGFR
mutations
Phase III
evidence
provided by
IPASS and
OPTIMAL
20,31
FLEX
21
BR21 and
TRIBUTE
35,36
Unknown
EGFR
Amplification
BR21 and
ISEL
33,48,49,50
FLEX
21
Limited
retrospective
data
61,62
Unknown
KRAS
Mutations
BR21,
INTEREST
and
SATURN
43,73,74
FLEX and
BMS099
57,70
Retrospective
work and
phase III
adjuvant
study data
(BR10)
67,68
Unknown
TGF-α
BR21
79
Unknown Retrospective
work from
BR21
79
Unknown
Amphiregulin
BR21
79
Unknown BR21
79
Unknown
Short
EGFR
Intron 1
repeats
Uncertain
Unknown Uncertain Retrospective
evidence
86
