Outcome of Patients with Platelet-Derived Growth Factor Receptor Alpha-Mutated Gastrointestinal Stromal Tumors in the Tyrosine Kinase Inhibitor Era
Outcome of Patients with Platelet-Derived Growth Factor Receptor Alpha-Mutated Gastrointestinal Stromal Tumors in the Tyrosine Kinase Inhibitor Era
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DOI：
10.1158/1078-0432.ccr-11-3025
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发表时间：
2012-08-15
影响因子：
11.5
通讯作者：
Hohenberger, Peter
中科院分区：
文献类型：
--
作者：
Cassier, Philippe A.;Fumagalli, Elena;Hohenberger, Peter
目的：血小板衍生生长因子受体- α (PDGFRA)突变在大约5%至7%的晚期胃肠道间质瘤（GIST）中发现。我们试图广泛评估伊马替尼在该亚组中的活性。实验设计：我们在GIST转诊中心进行了一项国际调查，以收集晚期pdgfr -突变的GIST患者接受伊马替尼治疗晚期疾病的临床数据。结果：纳入58例患者，其中34例为男性（59%），治疗开始时的中位年龄为61岁（范围19-83岁）。原发肿瘤为胃，40例（69%）。32例（55%）患者存在pdgfr - d842v替换，17例（29%）患者存在影响18外显子其他密码子的突变，9例（16%）患者存在其他外显子突变。57例患者可评估反应，2例（4%）完全缓解，8例（14%）部分缓解，23例（40%）病情稳定。31例可评估的D842V替代患者中没有一例出现缓解，而31例患者中有21例（68%）的最佳缓解是进展。D842V替代患者的中位无进展生存期为2.8[95%可信区间（CI）， 2.6-3.2]个月，其他PDGFRA突变患者的中位无进展生存期为28.5个月（95% CI, 5.4-51.6）。在46个月的随访中，D842V替代患者的中位总生存期为14.7个月，而非D842V突变患者的中位总生存期未达到。结论：这项研究是迄今为止对伊马替尼治疗的晚期pdgfr -突变的gist患者报道的最大的研究。我们的数据证实，伊马替尼对18外显子D842V替换的患者亚组几乎没有疗效，而其他突变似乎对伊马替尼敏感。临床癌症研究；18 (16);4458 - 64。AACR (C) 2012。
Purpose: Platelet-derived growth factor receptor-alpha (PDGFRA) mutations are found in approximately 5% to 7% of advanced gastrointestinal stromal tumors (GIST). We sought to extensively assess the activity of imatinib in this subgroup.Experimental Design: We conducted an international survey among GIST referral centers to collect clinical data on patients with advanced PDGFRA-mutant GISTs treated with imatinib for advanced disease.Results: Fifty-eight patients were included, 34 were male (59%), and median age at treatment initiation was 61 (range, 19-83) years. The primary tumor was gastric in 40 cases (69%). Thirty-two patients (55%) had PDGFRA-D842V substitutions whereas 17 (29%) had mutations affecting other codons of exon 18, and nine patients (16%) had mutation in other exons. Fifty-seven patients were evaluable for response, two (4%) had a complete response, eight (14%) had a partial response, and 23 (40%) had stable disease. None of 31 evaluable patients with D842V substitution had a response, whereas 21 of 31 (68%) had progression as their best response. Median progression-free survival was 2.8 [95% confidence interval (CI), 2.6-3.2] months for patients with D842V substitution and 28.5 months (95% CI, 5.4-51.6) for patients with other PDGFRA mutations. With 46 months of follow-up, median overall survival was 14.7 months for patients with D842V substitutions and was not reached for patients with non-D842V mutations.Conclusions: This study is the largest reported to date on patients with advanced PDGFRA-mutant GISTs treated with imatinib. Our data confirm that imatinib has little efficacy in the subgroup of patients with D842V substitution in exon 18, whereas other mutations appear to be sensitive to imatinib. Clin Cancer Res; 18(16); 4458-64. (C)2012 AACR.