背景:间变性甲状腺癌(ATC)患者的不良预后与有限的有效治疗策略有关。多种抗血管生成酪氨酸激酶抑制剂(TKIs)已应用于ATC的后期治疗;然而,临床试验报告的结果存在争议.在这项研究中,我们重建了患者水平的数据,以汇总分析生存数据,回应,和不良事件。
方法:在线数据库(PubMed,WebofScience,Embase,和CochraneCENTRAL)于2023年9月3日进行了搜索。使用R软件结合“metaSurvival”和“meta”软件包重建生存曲线并总结反应率。主要终点是无进展生存期(PFS)和总生存期(OS)。次要终点是生存率,客观反应率(ORR),疾病控制率(DCR),和治疗相关的不良事件。
结果:纳入了涉及140例ATC患者的6项前瞻性临床试验。四种类型的TKIs(伊马替尼,帕唑帕尼,索拉非尼,和lenvatinib)被包括在内。当晚期ATC患者接受TKIs治疗时,中位OS为4.8个月,中位PFS为2.6个月.合并的ORR和DCR分别为9%和53%。高血压,食欲下降,皮疹,和淋巴细胞减少是最常见的≥3级治疗相关不良事件.
结论:单抗血管生成TKI治疗对晚期ATC患者的改善有限。抗血管生成TKI治疗联合化疗,放射治疗,或者免疫疗法可能是未来研究的方向。
BACKGROUND: The poor prognosis of anaplastic thyroid cancer (ATC) patients is associated with limited effective therapeutic strategies. Multiple antiangiogenesis tyrosine kinase inhibitors (TKIs) have been applied in later-line treatment of ATC; however, the results reported in clinical trials were controversial. In this study, we reconstructed the patient-level data to pooled-analyze the survival data, responses, and adverse events.
METHODS: Online databases (PubMed, Web of Science, Embase, and Cochrane CENTRAL) were searched on September 03, 2023. R software combined with the \"metaSurvival\" and \"meta\" packages were used to reconstruct the survival curves and summarize the response rates. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were survival rate, objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events.
RESULTS: Six prospective clinical trials involving 140 ATC patients were enrolled. Four types of TKIs (imatinib, pazopanib, sorafenib, and lenvatinib) were included. When advanced ATC patients were treated with the TKIs, the median OS was 4.8 months and the median PFS was 2.6 months. The pooled ORR and DCR were 9% and 53%. Hypertension, decreased appetite, rash, and lymphopenia were the most common grade ≥ 3 treatment-related adverse events.
CONCLUSIONS: Mono-anitangiogenesis TKI therapy showed limited improvements in treating advanced ATC patients. Combining antiangiogenesis TKI therapy with chemotherapy, radiotherapy, or immunotherapy could be the direction of future studies.