The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Adv Ther. 2023 Sep;40(9):3817-3829. doi: 10.1007/s12325-023-02576-0. Epub 2023 Jun 25.
Tyrosine-kinase inhibitors (TKIs) have become the standard treatment for patients with advanced gastrointestinal stromal tumor (GIST); however, secondary mutations can still drive disease progression. Studies have shown that ripretinib, a novel switch-control TKI, inhibits various primary and secondary drug-resistant mutations. There is a paucity of data on the effectiveness and safety of ripretinib in a real-world setting. This prospective, large-scale, real-world registry study aimed to evaluate the effectiveness and safety of ripretinib as a fourth-line treatment in Chinese patients with advanced GIST.
Patients ≥ 18 years of age having recurrent/metastatic GIST were enrolled. Key endpoints were median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) incidence. Univariate and multivariate analyses were conducted to identify various parameters associated with PFS.
A total of 240 patients were enrolled. After a median follow-up period of 6.5 months, the mPFS [95% confidence interval (CI)] was 7.70 (6.60, 8.60) months and the mOS was not reached. Multivariate analysis revealed association of Eastern Cooperative Oncology Group (ECOG) performance status score with PFS and superior benefits for non-gastric was observed as compared to gastric GISTs [hazard ratio (HR) 0.58, 95% CI (0.39-0.86)]. Disease control rate and tumor shrinkage (any magnitude) was 73% and 43%, respectively. Ripretinib was also effective in the subgroup of patients with different gene mutations. The toxicities were tolerable, and most reported AEs were alopecia (17.1%) and hand-foot syndrome (15.4%).
Ripretinib demonstrated effectiveness and a tolerable safety profile, making it a viable option as a fourth- or later-line treatment in Chinese patients with advanced GISTs, especially for non-gastric GISTs.
ClinicalTrials.gov identifier, NCT05697107.
酪氨酸激酶抑制剂（TKI）已成为晚期胃肠道间质瘤（GIST）患者的标准治疗方法；然而，继发性突变仍可导致疾病进展。研究表明，新型开关控制 TKI 瑞派替尼可抑制各种原发性和继发性耐药突变。在真实环境中，瑞派替尼的有效性和安全性数据很少。本前瞻性、大规模、真实世界登记研究旨在评估瑞派替尼作为中国晚期 GIST 四线治疗的有效性和安全性。
纳入年龄≥18 岁的复发性/转移性 GIST 患者。主要终点为中位无进展生存期（mPFS）、中位总生存期（mOS）和不良反应（AE）发生率。采用单变量和多变量分析确定与 PFS 相关的各种参数。
共纳入 240 例患者。中位随访 6.5 个月后，mPFS（95%置信区间 [CI]）为 7.70（6.60，8.60）个月，mOS 未达到。多变量分析显示，东部肿瘤协作组（ECOG）表现状态评分与 PFS 相关，非胃 GIST 比胃 GIST 观察到更好的获益（风险比 [HR] 0.58，95% CI [0.39-0.86]）。疾病控制率和肿瘤退缩（任何程度）分别为 73%和 43%。瑞派替尼在不同基因突变患者亚组中也有效。毒性可耐受，大多数报告的 AE 为脱发（17.1%）和手足综合征（15.4%）。
瑞派替尼具有有效性和可耐受的安全性特征，使其成为中国晚期 GIST 患者的第四线或更后线治疗的可行选择，特别是对于非胃 GIST。
ClinicalTrials.gov 标识符，NCT05697107。
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