Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

154 Applying Pharmacogenomics in Therapeutics
TABLE 6.4
PGx Biomarkers for the Selection of Cancer Therapy
PGx
Biomarker
EGFR (HER1)
in NSCLC
HER2/neu
(ErbB2) in
breast cancer
and gastric
tumor
Therapeutic
Agents
Erlotinib
(Tarceva ® ),
gefitinib
(Iressa ® )
Trastuzumab
(Herceptin ® ),
lapatinib
(Tykerb ® )
Mutations to Be
Detected Potential Clinical Impact ASCO or NCCN Guidelines
Activating tumor
EGFR mutations:
mainly deletions
in exon 19 and
L858R
Resistance tumor
mutation:
T790M
Use IHC or FISH
to detect HER2
gene
overexpression
The presence of EGFRactivating
mutations
predicts response to
gefitinib and erlotinib.
The presence of EGFR
T790M mutation predicts
resistance to gefitinib.
Overexpression of HER2
(+3 by IHC or FISH)
predicts response to
trastuzumab and lapatinib.
Recommends testing for EGFR mutations before use
of gefitinib or erlotinib. 40
Recommends testing HER2 expression for all breast
cancer tumors and to use trastuzumab for patients
with HER2 overexpression. 41
List lapatinib in combination with capecitabine as an
option for trastuzumab-refractory breast cancer
patients. 7
K-RAS in
metastatic
colon cancer
and SCCHN
Cetuximab
(Erbitux ® ),
panitumumab
(Vectibix ® )
Activating tumor
K-RAS
mutations:
mainly exon 2
codon 12 and 13
Presence of K-RAS
mutations predicts
nonresponse to cetuximab
and panitumumab.
Absence of K-RAS
mutations predicts
response to cetuximab and
panitumumab.
Recommends genotyping tumor tissue for K-RAS
mutation in all patients with metastatic colorectal
cancer. 42
Patients with known codon 12 and 13 K-RAS gene
mutation are unlikely to respond to EGFR inhibitors
and should not receive cetuximab. 42 (Continued)