Department of Gastrointestinal Surgery, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China.
Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Dis Markers. 2018 Aug 26;2018:1368617. doi: 10.1155/2018/1368617. eCollection 2018.
Sunitinib (a second-line chemotherapeutic agent that inhibits multiple kinases, including KIT and PDGFR) is widely used in imatinib-resistant patients with gastrointestinal stromal tumors (GISTs). However, diverse responses to sunitinib have been observed in the clinic. We aimed to evaluate whether the different GIST genotypes could be used to stratify patient response to sunitinib.
We searched the PubMed, Embase, and Cochrane databases and included English-language literature published up to August 31, 2017. Inclusion criteria were GIST patients with KIT exon 9, KIT exon 11, or PDGFRA mutations and those without KIT/PDGFRA mutations (termed the wild-type genotype) who were receiving sunitinib within a clinical trial, and the efficacy evaluation was clinical benefit rate (CBR), median progression-free survival (PFS), and overall survival (OS). Odds ratios (ORs) for CBR and hazard ratios (HRs) for PFS and OS with 95% confidence intervals (CIs) in sunitinib-treated GIST patients with different genotypes were compared.
Seven studies totaling 531 patients were included. Patients with KIT mutations showed an improved CBR to sunitinib compared to those with PDGFRA mutations. In particular, those with the KIT exon 9 or 11 mutation showed improved CBR over those with PDGFRA mutation. Moreover, GIST patients with the KIT exon 9 mutation showed improved CBR over those with the KIT exon 11 mutation. Patients without KIT/PDGFRA mutations (wild-type genotype) showed better CBR than those with PDGFRA mutations.
GIST genotypes may be useful for stratifying patient response to sunitinib after imatinib resistance.
舒尼替尼（一种抑制多种激酶的二线化疗药物，包括 KIT 和 PDGFR）广泛用于伊马替尼耐药的胃肠道间质瘤（GIST）患者。然而，临床观察到对舒尼替尼的反应存在差异。我们旨在评估不同的 GIST 基因型是否可用于分层患者对舒尼替尼的反应。
我们检索了 PubMed、Embase 和 Cochrane 数据库，并纳入截至 2017 年 8 月 31 日发表的英文文献。纳入标准为接受临床试验中舒尼替尼治疗的 KIT 外显子 9、KIT 外显子 11 或 PDGFRA 突变的 GIST 患者，以及无 KIT/PDGFRA 突变（称为野生型基因型）的 GIST 患者，疗效评估为临床获益率（CBR）、中位无进展生存期（PFS）和总生存期（OS）。比较不同基因型的舒尼替尼治疗 GIST 患者的 CBR 比值比（OR）和 PFS 及 OS 的 HR（95%CI）。
共纳入 7 项研究，总计 531 例患者。与 PDGFRA 突变相比，KIT 突变的患者对舒尼替尼的 CBR 更高。特别是，与 PDGFRA 突变相比，KIT 外显子 9 或 11 突变的患者 CBR 更高。此外，KIT 外显子 9 突变的 GIST 患者的 CBR 高于 KIT 外显子 11 突变的患者。无 KIT/PDGFRA 突变（野生型基因型）的患者的 CBR 优于 PDGFRA 突变的患者。
GIST 基因型可能有助于分层患者对伊马替尼耐药后的舒尼替尼反应。
