Department of oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, P. R. China.
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Clin Endocrinol (Oxf). 2024 Apr;100(4):379-388. doi: 10.1111/cen.15027. Epub 2024 Feb 13.
The poor overall prognosis of radioiodine refractory thyroid cancer is an inevitable challenge in managing this disease. A series of trials have demonstrated the antitumor activity of tyrosine kinase inhibitors (TKIs) in radioiodine refractory differentiated thyroid cancer (RAIR-DTC). However, the available evidence cannot determine the optimal choice of TKI in RAIR-DTC.
This study searched PubMed, EMBASE, Cochrane databases, and the ClinicalTrials website. The Cochrane bias risk tool was used to assess the risk of bias, and to evaluate randomized clinical trials (RCT) of RAIR-DTC patients treated with the TKI system. Outcomes, including progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were reported.
Seven studies involving 1310 patients with RAIR-DTC was conducted to compare the PFS and OS of various TKI monotherapies with placebo. The results showed that all TKI monotherapies had a statistically significant benefit in terms of PFS compared with placebo, with lenvatinib demonstrating the greatest benefit (hazard ratio [HR] 0.19, 95% credible interval [CrI] 0.14-0.25). In terms of OS, only apatinib (HR 0.42, 95% CrI 0.18-0.97) and anlotinib (HR 0.36, 95% CrI 0.18-0.73) showed statistically significant benefits compared with placebo. TKIs also had a higher incidence of AEs of grade 3 or higher compared with placebo. The findings suggest that lenvatinib may be the preferred TKI for the treatment of RAIR-DTC, although its high incidence of AEs should be considered. The results also indicate that TKI treatment may be similarly effective in RAIR-DTC patients with BRAF or RAS mutations and in those with papillary or follicular subtypes of the disease, regardless of prior TKI treatment.
The results of this meta-analysis suggest that targeted therapy with TKIs may be beneficial for patients with radioiodine-refractory advanced or metastatic differentiated thyroid cancer. Among the TKIs analyzed, lenvatinib appeared to be the most effective at improving PFS, although it also had the highest incidence of AEs. Further research through direct randomized controlled trials is needed to determine the optimal choice of TKI for treating patients with RAIR-DTC. This study is beneficial for formulating patients' treatment plans and guides clinicians' decision-making.
放射性碘难治性甲状腺癌的总体预后较差,这是管理这种疾病的必然挑战。一系列试验已经证明了酪氨酸激酶抑制剂(TKI)在放射性碘难治性分化型甲状腺癌(RAIR-DTC)中的抗肿瘤活性。然而,现有证据无法确定 RAIR-DTC 中 TKI 的最佳选择。
本研究检索了 PubMed、EMBASE、Cochrane 数据库和 ClinicalTrials 网站。使用 Cochrane 偏倚风险工具评估 RAIR-DTC 患者接受 TKI 系统治疗的随机临床试验(RCT)的偏倚风险,并评估其结果,包括无进展生存期(PFS)、总生存期(OS)和不良事件(AEs)。
共纳入 7 项研究,涉及 1310 例 RAIR-DTC 患者,比较了各种 TKI 单药治疗与安慰剂的 PFS 和 OS。结果表明,与安慰剂相比,所有 TKI 单药治疗在 PFS 方面均具有统计学意义上的获益,仑伐替尼获益最大(风险比[HR]0.19,95%可信区间[CrI]0.14-0.25)。在 OS 方面,只有阿帕替尼(HR 0.42,95% CrI 0.18-0.97)和安罗替尼(HR 0.36,95% CrI 0.18-0.73)与安慰剂相比具有统计学意义上的获益。与安慰剂相比,TKI 还导致更高的 3 级或更高级别不良事件发生率。研究结果表明,仑伐替尼可能是治疗 RAIR-DTC 的首选 TKI,但应考虑其较高的不良事件发生率。结果还表明,TKI 治疗在伴有 BRAF 或 RAS 突变以及伴有乳头状或滤泡状亚型的 RAIR-DTC 患者中可能同样有效,无论之前是否接受过 TKI 治疗。
这项荟萃分析的结果表明,靶向治疗 TKI 可能对放射性碘难治性晚期或转移性分化型甲状腺癌患者有益。在分析的 TKI 中,仑伐替尼在改善 PFS 方面似乎最有效,尽管它也有最高的不良事件发生率。需要通过直接的随机对照试验进一步研究,以确定治疗 RAIR-DTC 患者的 TKI 的最佳选择。本研究有助于制定患者的治疗计划,并指导临床医生的决策。