Biomedical Engineering Reference
In-Depth Information
to identify predictors of benefit. With regards to
KRAS
mutations,
neither the FLEX trial or BMS-099 trials found that
mutations
were predictive for cetuximab efficacy when combined with first-
line chemotherapy in advanced NSCLC.
KRAS
57,70
Two meta-analyses have been performed evaluating activating
KRAS
mutations and response to EGFR TKIs. The first analyzed 17
studies for a total of 165
mutant patients while the second
evaluated 22 studies for a total of 231
KRAS
mutant patients. Both
studies found a lack of response to TKIs in patients with
KRAS
KRAS
mutations, although this did not result in a significant difference
in PFS or OS.
71,72
In a multivariate analysis, the NCIC BR21 study
found that
KRAS
mutations were not predictive of a differential
treatment effect.49
The INTEREST trial found no differences between
treatments in OS, PFS or response rate according to
49
KRAS
mutation
73
status in patients who received gefitinib.
The Sequential Tarceva in
Unresectable NSCLC (SATURN) trial, which evaluated maintenance
erlotinib in patients without progression of disease after 4 cycles
of first-line cytotoxic chemotherapy, found no differences in PFS
between wild-type and mutant
74
mutation
status in the ISEL trial could not be evaluated. It should be noted that
most of these evaluations were performed on only a fraction of trial
participants due to a lack of tissue availability. At the current time,
there is no evidence suggesting that
KRAS
patients.
KRAS
KRAS
mutations affect EGFR TKI
benefit in NSCLC.
6.9
EGFR Ligands
Ligands that target the epidermal growth factor receptor family
consist of three main groups. The first group binds specifically to
EGFR and consists of EGF, TGF-α, and amphiregulin. The second group
has specificity for both EGFR and HER4 and includes betacellulin
and heparin-binding EGF as members. The third group binds HER3
and HER4 and is composed of the neuregulins.
75
Relative to the evaluation of other EGFR biomarkers, there is a
paucity of data on the prognostic and predictive implications of the
EGFR ligands. Within the EGF ligand family, TGF-α and amphiregulin
have been studied more extensively, either as circulating ligands
within the blood or within the tumor. However, most work has been
undertaken in single cohorts of patients with inconsistent results
