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

IF 4.4 3区医学 Q2 ONCOLOGY

Targeted Oncology Pub Date : 2024-07-01 Epub Date: 2024-05-18 DOI:10.1007/s11523-024-01067-8

Tai Van Nguyen, Diaddin Hamdan, Géraldine Falgarone, Kien Hung Do, Quang Van Le, Frédéric Pamoukdjian, Guilhem Bousquet

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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 (I² = 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.

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癌症患者中与抗血管生成酪氨酸激酶抑制剂相关的毒性：系统回顾与元分析》。

背景：靶向血管生成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（TKIs）的毒性，有许多问题尚未解决：我们进行了一项荟萃分析，以评估不同抗血管生成酪氨酸激酶抑制剂在癌症患者以及包括肾细胞癌患者在内的相关亚人群中的毒性发生率：我们检索了截至 2023 年 11 月的 MEDLINE 和 Cochrane Library 数据库。符合条件的临床试验必须报告与目前批准的七种抗血管生成 TKIs 单药疗法之一相关的≥3 级毒性。PROSPERO（CRD42023411946）采用了系统综述和荟萃分析首选报告项目（PRISMA）方法：421项符合条件的研究共纳入了56895名接受抗血管生成TKI单药治疗的癌症患者。确定了 24 种不同的癌症类型，主要是肾细胞癌（占患者总数的 41.9%）。抗血管生成 TKI 包括索拉非尼（34.5% 的患者）、舒尼替尼（30.5%）、瑞戈非尼（10.7%）、帕唑帕尼（9.4%）、卡博赞替尼（7.7%）、阿昔替尼（4.3%）和来伐替尼（2.9%）。汇总的3级和4级毒性发生率为56.1%（95%置信区间为53.5-58.6），研究间异质性明显（I2 = 96.8%）。根据TKI类型、癌症类型和特定患者特征的不同，毒性情况也有很大差异。尤其是亚洲患者和老年人的严重毒性发生率较高，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，尤其是转移性RCC患者，不同的治疗方案在毒性方面没有显著差异：这项荟萃分析强调了抗血管生成 TKI 单一疗法的毒性特征，从而为根据患者的年龄、种族、合并症和合并用药选择抗血管生成 TKI 提出了高水平的建议，以实现个性化治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.