Efficacy of Imatinib in Patients with Platelet-Derived Growth Factor Receptor Alpha-Mutated Gastrointestinal Stromal Tumors.
Efficacy of Imatinib in Patients with Platelet-Derived Growth Factor Receptor Alpha-Mutated Gastrointestinal Stromal Tumors.
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DOI：
10.4143/crt.2015.015
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发表时间：
2016-04
影响因子：
4.6
通讯作者：
Kang YK
中科院分区：
文献类型：
--
作者：
Yoo C;Ryu MH;Jo J;Park I;Ryoo BY;Kang YK
携带血小板衍生生长因子受体α (PDGFRA)突变的胃肠道间质瘤（gist）的发生率较低，因此需要进一步研究伊马替尼在该亚组中的疗效。2000年1月至2012年6月期间接受伊马替尼作为晚期疾病主要治疗的pdgfr突变GIST患者来自韩国首尔牙山医疗中心的GIST登记。823例患者的KIT和PDGFRA基因分型发现18例（2%）PDGFRA突变患者接受一线伊马替尼治疗。外显子18 D842V替换、非D842V外显子18突变和外显子12突变分别在9例（50%）、4例（22%）和5例（28%）患者中检测到。D842V突变与非D842V突变患者的客观有效率差异有统计学意义（0% [0/5]vs. 71% [5/7], p=0.03）。在所有患者中，中位无进展生存期（PFS）和总生存期（OS）分别为24.8个月（95%可信区间[CI]， 0.0至57.2）和51.2个月（95% CI， 37.1至65.3）。值得注意的是，与非d842v pdgfr突变的gist患者相比，d842v突变的gist患者的PFS更差：中位3.8个月（95% CI， 1.4至6.3）对29.5个月（95% CI， 18.3至40.7）（p < 0.001）。与非D842V PDGFRA突变患者相比，D842V突变患者的OS较差：中位25.2个月（95% CI， 12.7至37.8）vs 59.8个月（95% CI， 43.0至76.5）（p=0.02）。伊马替尼对非D842V pdgfr突变的gist有活性，而含有D842V突变的gist主要对伊马替尼耐药。
The incidence of gastrointestinal stromal tumors (GISTs) harboring platelet-derived growth factor receptor alpha (PDGFRA) mutations is low, therefore further investigation of the efficacy of imatinib in this subgroup was needed. Patients with PDGFRA-mutant GISTs who received imatinib as primary therapy for advanced disease between January 2000 and June 2012 were identified from the GIST registry of Asan Medical Center, Seoul, Korea. KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Exon 18 D842V substitution, non-D842V exon 18 mutations, and exon 12 mutations were detected in nine (50%), four (22%), and five (28%) patients, respectively. Objective response rate differed significantly between patients with the D842V mutation and those with non-D842V mutations (0% [0/5] vs. 71% [5/7], p=0.03). In all patients, median progression-free survival (PFS) and overall survival (OS) was 24.8 months (95% confidence interval [CI], 0.0 to 57.2) and 51.2 months (95% CI, 37.1 to 65.3), respectively. Significantly, poorer PFS was observed for patients with D842V-mutant GISTs than those with non-D842V PDGFRA-mutant GISTs: median 3.8 months (95% CI, 1.4 to 6.3) versus 29.5 months (95% CI, 18.3 to 40.7) (p < 0.001). Patients with the D842V mutation had poorer OS than those with non-D842V PDGFRA mutations: median 25.2 months (95% CI, 12.7 to 37.8) versus 59.8 months (95% CI, 43.0 to 76.5) (p=0.02). Imatinib is active against non-D842V PDGFRA-mutant GISTs, whereas GISTs harboring the D842V mutation are primarily resistant to imatinib.