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

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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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Acknowledgments

The authors thank Ms. Angela Swaine for the English language revision.

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Authors and Affiliations

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

    Tai Van Nguyen, Diaddin Hamdan, Géraldine Falgarone, Frédéric Pamoukdjian & Guilhem Bousquet

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

    Tai Van Nguyen & Kien Hung Do

  3. Hanoi Medical University, Hanoi, Vietnam

    Tai Van Nguyen & Quang Van Le

  4. Université Sorbonne Paris Nord, 9 Avenue Jean Baptiste Clément, 93439, Villetaneuse, France

    Tai Van Nguyen, Diaddin Hamdan, Géraldine Falgarone, Frédéric Pamoukdjian & Guilhem Bousquet

  5. Department of Medical Oncology, Hôpital de la Porte Verte, 78000, Versailles, France

    Diaddin Hamdan

  6. Assistance Publique Hôpitaux de Paris, Hôpital Avicenne, Unité de Médecine Ambulatoire, 93008, Bobigny, France

    Géraldine Falgarone

  7. Service de Médecine Gériatrique, Assistance Publique Hôpitaux de Paris, Hôpital Avicenne, 93008, Bobigny, France

    Frédéric Pamoukdjian

  8. Service d’oncologie Médicale, Assistance Publique Hôpitaux de Paris, Hôpital Avicenne, 93008, Bobigny, France

    Guilhem Bousquet

  9. UMR_S942 Inserm, Université de Paris, Université Sorbonne Paris Nord, UFR SMBH, 1 rue Chablis, 93000, Bobigny, France

    Guilhem Bousquet

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  1. Tai Van Nguyen
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Correspondence to Guilhem Bousquet.

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Funding

This study was supported by Bourse d’Excellence de l’Ambassade de France au Viet Nam (grant number 133125S).

Conflicts of Interest

Tai Van Nguyen, Diaddin Hamdan, Géraldine Falgarone, Kien Hung Do, Quang Van Le, Frédéric Pamoukdjian, and Guilhem Bousquet declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Authors’ Contributions

Conception and design: TVN and GB. Administrative support: DH, QVL, and GB. Collection and assembly of data: TVN, DH and GB. Data analysis and interpretation: All authors. Manuscript draft: TVN, DH, GF, and GB. Final approval of manuscript: All authors.

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Van Nguyen, T., Hamdan, D., Falgarone, G. et al. Anti-Angiogenic Tyrosine Kinase Inhibitor-Related Toxicities Among Cancer Patients: A Systematic Review and Meta-Analysis. Targ Oncol (2024). https://doi.org/10.1007/s11523-024-01067-8

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