抗血管生成酪氨酸激酶抑制剂相关毒性在癌症患者中的系统评价和荟萃分析。

Anti-Angiogenic Tyrosine Kinase Inhibitor-Related Toxicities Among Cancer Patients: A Systematic Review and Meta-Analysis.

机构信息

Université Paris Cité, INSERM UMR_S942, MASCOT, 75006, Paris, France.

Department of Medical Oncology I, Vietnam National Cancer Hospital, Hanoi, Vietnam.

出版信息

Target Oncol. 2024 Jul;19(4):533-545. doi: 10.1007/s11523-024-01067-8. Epub 2024 May 18.

DOI:10.1007/s11523-024-01067-8

PMID:38761350

Abstract

BACKGROUND: Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of anti-angiogenic tyrosine kinase inhibitors (TKIs). OBJECTIVE: We performed a meta-analysis to assess the toxicity prevalence of the different anti-angiogenic TKIs among cancer patients and in subpopulations of interest including patients with renal cell carcinoma. PATIENTS AND METHODS: We searched the MEDLINE and Cochrane Library databases to November 2023. Clinical trials were eligible if they set out to report the grade ≥3 toxicities related to one of the seven currently approved anti-angiogenic TKIs as monotherapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was applied with PROSPERO (CRD42023411946). RESULTS: The 421 eligible studies included a total of 56,895 cancer patients treated with anti-angiogenic TKI monotherapy. Twenty-four different cancer types were identified, mainly renal cell carcinoma (41.9% of the patients). The anti-angiogenic TKI was sorafenib (34.5% of the patients), sunitinib (30.5%), regorafenib (10.7%), pazopanib (9.4%), cabozantinib (7.7%), axitinib (4.3%), and lenvatinib (2.9%). The pooled prevalence of grade 3 and 4 toxicities was 56.1% (95% confidence interval 53.5-58.6), with marked between-study heterogeneity (I = 96.8%). Toxicity profiles varied considerably depending on the type of TKI, the cancer type, and the specific patient characteristics. In particular, Asian patients and elderly people had higher prevalences of severe toxicities, with pazopanib being the best-tolerated drug. For patients treated with sunitinib, particularly those with metastatic RCC, there was no significant difference in terms of toxicity according to the regimen schedule. CONCLUSIONS: This meta-analysis highlights the toxicity profiles of anti-angiogenic TKI monotherapies, and thus enables high-level recommendations for the choice of anti-angiogenic TKIs on the basis of the patient's age, ethnicity, comorbidities, and comedications, for personalized treatment.

摘要

背景：针对血管生成的靶向治疗已成为治疗各种晚期癌症的主要治疗方法。关于抗血管生成酪氨酸激酶抑制剂（TKI）的毒性，仍存在许多悬而未决的问题。

目的：我们进行了一项荟萃分析，以评估不同抗血管生成 TKI 在癌症患者中的毒性发生率，并在包括肾细胞癌患者在内的感兴趣的亚人群中进行评估。

患者和方法：我们检索了 MEDLINE 和 Cochrane 图书馆数据库至 2023 年 11 月。如果临床试验旨在报告与七种目前批准的抗血管生成 TKI 之一相关的≥3 级毒性，则符合纳入标准，这些毒性作为单一疗法。采用 Preferred Reporting Items for Systematic Reviews and Meta-Analyses（PRISMA）方法，并使用 PROSPERO（CRD42023411946）进行注册。

结果：421 项符合条件的研究共纳入了 56895 名接受抗血管生成 TKI 单一疗法治疗的癌症患者。确定了 24 种不同的癌症类型，主要是肾细胞癌（患者的 41.9%）。抗血管生成 TKI 是索拉非尼（患者的 34.5%）、舒尼替尼（30.5%）、regorafenib（10.7%）、帕唑帕尼（9.4%）、卡博替尼（7.7%）、阿昔替尼（4.3%）和仑伐替尼（2.9%）。3 级和 4 级毒性的总体发生率为 56.1%（95%置信区间 53.5-58.6），研究间存在显著的异质性（I=96.8%）。毒性谱因 TKI 类型、癌症类型和特定患者特征而有很大差异。特别是，亚洲患者和老年人发生严重毒性的比例较高，而帕唑帕尼是耐受性最好的药物。对于接受舒尼替尼治疗的患者，特别是转移性肾细胞癌患者，根据治疗方案，毒性方面没有显著差异。

结论：这项荟萃分析强调了抗血管生成 TKI 单一疗法的毒性谱，因此可以根据患者的年龄、种族、合并症和合并用药情况，为选择抗血管生成 TKI 提供高级别的建议，以实现个体化治疗。