Kinase mutations and imatinib mesylate response for 64 Taiwanese with advanced GIST: preliminary experience from Chang Gung Memorial Hospital.
OBJECTIVE
Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutation of kit or platelet-derived growth factor receptor alpha (PDGFRA), which are therapeutic targets for imatinib. Results of 64 Taiwanese with advanced GIST treated with imatinib were reported.


METHODS
Between 2001 and May 2006, a prospective, non-randomized, and a single center trial containing 64 Taiwanese patients with advanced GIST treated with imatinib was conducted. Each tumor was investigated for mutations of kit or PDGFRA.


RESULTS
The median follow-up time after imatinib administration was 16.1 months. 12 patients (18.8%) had complete response (CR), 24 (37.5%) had a partial response (PR), 12 stationary disease (18.8%), 16 progressive disease (25.0%). The 64 Taiwanese with advanced GIST had an estimated median survival of 48.0 months and 4-year survival rate for 76.1%. Kit mutation was found in 49 of 54 (90.7%) test patients and five of them had no mutation (9.3%). No PDGFRA mutant was identified. In 40 patients harboring kit exon 11 mutations, the CR and PR rates (ORR) were 57.5% , nine patients with tumors containing kit exon 9 mutation had ORR rates of 22.2%, and five patients with no mutation had ORR rates of 60.0% (not significant; P = 0.149).


CONCLUSIONS
Activated mutation of kit constituted 90.7% genetic alteration of Taiwanese with advanced GIST and no PDGFRA mutation was detected. Imatinib induced a sustained objective response in more than half of Taiwan advanced GIST patients. ORR did not differ between patients whose GISTs had no mutation, kit exon 9, and 11 mutations.
Yeh
Chun-Nan
CN
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan. ycn@adm.cgmh.org.tw
Chen
Tsung-Wen
TW
Lee
Hsiang-Lin
HL
Liu
Yu-Yin
YY
Chao
Tzu-Chieh
TC
Hwang
Tsann-Long
TL
Jan
Yi-Yin
YY
Chen
Miin-Fu
MF
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D013624:Taiwan / Q000453:epidemiology
D000970:Antineoplastic Agents; D001549:Benzamides; D004273:DNA, Neoplasm; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha