Kinase mutations and efficacy of imatinib in Korean patients with advanced gastrointestinal stromal tumors.
OBJECTIVE
This study analyzed the relationship between treatment outcome and kinase mutational status in Korean patients with advanced gastrointestinal stromal tumors (GISTs).


METHODS
Clinical data were collected from 113 consecutive patients with metastatic or unresectable GISTs treated with imatinib from June 2001 through June 2005 at five institutions in Korea. KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were examined.


RESULTS
The median patient age was 57 years (range, 31-82 years). The overall response rate was 67.2%. KIT mutations were found in exon 11 (n = 92, 81.4%) and exon 9 (n = 10, 8.8%). One patient had a PDGFRA exon 18 mutation. The overall mutation rate was 91.2%. Response rates were 68.4%, 50.0%, and 80.0% in patients with KIT exon 11 mutations, KIT exon 9 mutations, and no kinase mutations, respectively. With a median follow-up of 49.0 months, the median progression-free survival (PFS) time was 42.0 months and median overall survival (OS) time was not reached. PFS and OS times did not differ significantly according to KIT genotype.


CONCLUSIONS
This study was unable to find an association between KIT mutational status and clinical outcome of imatinib in Korean patients with advanced GISTs. There was a trend toward better outcomes for patients with wild-type KIT or exon 11 mutations compared with exon 9 mutations, although this was not statistically significant. Compared with previous studies in western populations, these results suggest that ethnic differences may influence the relationship between KIT genotype and clinical outcome to imatinib.
Section of Oncology, Department of Medicine, Asan Medical Center, 388-1 Poongnap-dong, Songpa-ku, Seoul, Korea. ykkang@amc.seoul.kr
Tae Won
TW
Kim
Min-Hee
MH
Ryu
Heungnam
H
Lee
Sun Jin
SJ
Sym
Jae-Lyun
JL
Lee
Heung Moon
HM
Chang
Young Suk
YS
Park
Kyung Hee
KH
Lee
Won Ki
WK
Kang
Dong Bok
DB
Shin
Yung-Jue
YJ
Bang
Jung Shin
JS
Lee
Yoon-Koo
YK
Kang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha; D051057:Proto-Oncogene Proteins c-akt