Purpose. To assess the efficacy of imatinib for different tumor genotypes in Korean patients with advanced gastrointestinal stromal tumors (GIST). Material and methods. Clinical data were collected from 370 consecutive patients with locally advanced unresectable, metastatic, or recurrent GIST treated with imatinib 400 mg/day between August 2001 and December 2007 at 20 Korean institutions. Tumor genotypes were determined for 290 patients by direct DNA sequencing of KIT exons 9, 11, 13, and 17, and PDGFRA exons 12, 14, and 18. Results. Of 290 patients assessed for genotype, 261 (90.0%) had mutations in KIT: 222 (76.6%) in exon 11, 35 (12.1%) in exon 9 and two each (0.7%) for exons 13 and 17. Four patients (1.4%) had mutations in the PDGFRA gene: one in exon 12, and three in exon 18. Twenty-five patients (8.6%) had no detectable mutations. The best responses of the 235 patients with measurable lesions were: 15 complete response (6.4%), 126 partial response (53.5%), 86 stable disease (36.6%), and eight progressive disease (3.4%). Patients with KIT exon 9 mutations, compared with patients with KIT exon 11 mutations, had a lower objective response rate (36.7% vs. 63.6%, p = 0.007) and a shorter progression-free survival (median 28.7 months vs. 49.4 months, p = 0.001). No statistical difference in overall survival was observed between these genotypes. Conclusion. This study confirms that imatinib efficacy is dependent on genotype in Korean GIST patients, consistent with results demonstrated by Western patients with GIST.
Bibliographical noteFunding Information:
We thank co-investigators (Yeul Hong Kim, Seong Hoon Shin, Hun-Mo Ryoo, Young Jin Choi, Seok Yun Kang, Sung Sook Lee, Hyeok Shim, Dae Young Zang) for collection of clinical data and provision of study materials. And we thank Ms Sun-young Hwangbo who is an administrative secretary of the KGSG. The authors acknowledge Robert Gillespie, PhD, of Chameleon Communications International, who provided editorial assistance with funding from Novartis Pharmaceuticals. Supported in part by Novartis Pharma AG, Basel, Switzerland.