Department of Pharmacy, Kunming Yan'an Hospital, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, 650051, China.
Department of Pharmacy, Tumor Hospital of Yunnan Province, Third Affiliated Hospital To Kunming Medical University, Kunming, 650118, China.
Adv Ther. 2021 Jan;38(1):399-412. doi: 10.1007/s12325-020-01545-1. Epub 2020 Nov 1.
The prospect of targeted therapies for advanced gastrointestinal stromal tumors (GISTs) has been dramatically transformed after encouraging results achieved in recent clinical trials. At present, the number of second- and third-line treatments are increasing, although the challenge is to take into account the differences between these interventions. Therefore, our goal is to evaluate the investigation of different regimens currently used in GISTs based on findings from phase II or phase III randomized controlled trials (RCTs), and then indirectly compare the effectiveness and safety of the available therapies.
The qualified literatures in relevant sources were searched systematically. Studies to identify RCTs of which main endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or more adverse events (AEs) in patients with GISTs were considered for inclusion.
Eight RCTs met our inclusion criteria, which involved 2351 patients. For PFS, compared with placebo, imatinib, and sunitinib, regorafenib (HR = 0.12, 95% CI 0.07-0.23; HR = 0.27, 95% CI 0.19-0.39; HR = 0.36, 95% CI 0.19-0.72, respectively) and ripretinib (HR = 0.15, 95% CI 0.09-0.25; HR = 0.33, 95% CI 0.16-0.68; HR = 0.44, 95% CI 0.25-0.78, respectively) were significantly correlated with the improvement of PFS, and regorafenib may be the preferred option according to the analysis of treatment rankings. For OS, compared with placebo, imatinib, and sunitinib, masitinib (HR = 0.13, 95% CI 0.04-0.44; HR = 0.13, 95% CI 0.04-0.51; HR = 0.27, 95%CI 0.09-0.84) and ripretinib (HR = 0.36, 95% CI 0.21-0.62; HR = 0.36, 95% CI 0.16-0.80; HR = 0.18, 95% CI 0.09-0.36, respectively) were significantly more effective, and masitinib may be the best choice according to treatment ranking analysis. Statistically, regorafenib can be considered to be the highest in high-grade AEs, while the rate of severe AEs of ripretinib and masitinib was likely the lowest.
Our results show that ripretinib has the most favorable balance between effectiveness and tolerability among the different treatment regimens for GISTs.
在最近的临床试验中取得令人鼓舞的结果后，胃肠道间质瘤（GIST）的靶向治疗前景发生了巨大变化。目前，二线和三线治疗的数量正在增加，尽管挑战在于考虑这些干预措施之间的差异。因此，我们的目标是根据 II 期或 III 期随机对照试验（RCT）的结果评估目前在 GIST 中使用的不同方案的研究，并间接比较现有治疗方法的有效性和安全性。
系统地搜索相关来源的合格文献。纳入主要终点为无进展生存期（PFS）、总生存期（OS）和 GIST 患者 3 级或更高级别不良事件（AE）的 RCT 研究。
符合纳入标准的 8 项 RCT 共纳入 2351 例患者。在 PFS 方面，与安慰剂相比，伊马替尼和舒尼替尼，regorafenib（HR=0.12，95%CI 0.07-0.23；HR=0.27，95%CI 0.19-0.39；HR=0.36，95%CI 0.19-0.72）和 ripretinib（HR=0.15，95%CI 0.09-0.25；HR=0.33，95%CI 0.16-0.68；HR=0.44，95%CI 0.25-0.78）与 PFS 改善显著相关，根据治疗排名分析，regorafenib 可能是首选。在 OS 方面，与安慰剂相比，伊马替尼和舒尼替尼，masitinib（HR=0.13，95%CI 0.04-0.44；HR=0.13，95%CI 0.04-0.51；HR=0.27，95%CI 0.09-0.84）和 ripretinib（HR=0.36，95%CI 0.21-0.62；HR=0.36，95%CI 0.16-0.80；HR=0.18，95%CI 0.09-0.36）的效果显著更好，根据治疗排名分析，masitinib 可能是最佳选择。从统计学上看，regorafenib 可被认为是 GIST 不同治疗方案中高级别 AE 发生率最高的药物，而 ripretinib 和 masitinib 的严重 AE 发生率可能最低。
我们的结果表明，在 GIST 的不同治疗方案中，ripretinib 在有效性和耐受性之间具有最有利的平衡。
