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Updated: Jun 26, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Anti-Angiogenic Tyrosine Kinase Inhibitor-Related Toxicities Among Cancer Patients: A Systematic Review and
Tai Van Nguyen1,2,3,4, Diaddin Hamdan1,4,5, Géraldine Falgarone1,4,6
1Université Paris Cité, INSERM UMR_S942, MASCOT, 75006, Paris, France.
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.
Insights
This meta-analysis reveals that anti-angiogenic tyrosine kinase inhibitors (TKIs) have a 56.1% prevalence of severe toxicities in cancer patients. Toxicity varies by TKI, cancer type, and patient factors, informing personalized treatment choices.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Targeting angiogenesis is crucial for advanced cancer therapy.
- Anti-angiogenic tyrosine kinase inhibitors (TKIs) are widely used but have unresolved toxicity concerns.
Conclusions:
- Anti-angiogenic TKI monotherapies exhibit significant toxicity profiles.
- Findings support personalized TKI selection based on patient age, ethnicity, comorbidities, and comedications.
- Recommendations for optimized treatment strategies are enabled by understanding TKI-specific toxicities.
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