Hypertension as a Comorbidity in Patients on Targeted Therapy
DOI:
https://doi.org/10.5281/zenodo.18749868Palavras-chave:
Inibidores de Tirosina Quinase, Inibidores de Checkpoint Imunológico, Inibidores da Tirosina Quinase de BrutonEfeitos Adversos Cardiovasculares, ComorbidadeResumo
Targeted therapies have transformed cancer treatment but are associated with cardiovascular adverse effects, particularly hypertension. The incidence and underlying mechanisms of this comorbidity vary across different therapeutic classes. This study aims to synthesize the available evidence regarding the incidence, severity, and potential mechanisms of hypertension in patients receiving different classes of targeted therapies. Narrative review based exclusively on the analysis of seven provided studies, including phase 3 clinical trials, phase 1/2 studies, and mechanistic reviews. Grade 3 or higher hypertension occurred in 62–65% of patients treated with cabozantinib, 13.7% with ivonescimab, 6% with pembrolizumab, and 14.2% with pirtobrutinib. Proposed mechanisms include inhibition of additional kinases containing cysteine residues in the catalytic domain. Cardiovascular adverse effects persisted beyond the initial treatment period. Hypertension represents a consistent and clinically significant comorbidity in patients receiving targeted therapy, with variable incidence depending on the therapeutic class, thereby justifying prolonged cardiovascular surveillance.
Referências
1. Chan JA, Geyer S, Zemla T, Knopp MV, Behr S, Pulsipher S, et al. Phase 3 trial of cabozantinib to treat advanced neuroendocrine tumors. N Engl J Med. 2025 Feb 13;392(7):653-665.
2. Shyam Sunder S, Sharma UC, Pokharel S. Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management. Signal Transduct Target Ther. 2023 Jul 7;8(1):262.
3. Estupiñán HY, Berglöf A, Zain R, Smith CIE. Comparative analysis of BTK inhibitors and mechanisms underlying adverse effects. Front Cell Dev Biol. 2021 Mar 11;9:630942.
4. O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022 Oct;23(10):1274-1286.
5. Tocchetti CG, Farmakis D, Koop Y, Andres MS, Couch LS, Formisano L, et al. Cardiovascular toxicities of immune therapies for cancer – a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology. Eur J Heart Fail. 2024 Oct;26(10):2055-2076.
6. Frentzas S, Austria Mislang AR, Lemech C, Nagrial A, Underhill C, Wang W, et al. Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 19;12(4):e008037.
7. Mato AR, Woyach JA, Brown JR, Ghia P, Patel K, Eyre TA, et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023 Jul 6;389(1):33-44.
Downloads
Arquivos adicionais
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2026 Lucas Rossetti de Almeida, Luiz Felipe Rodrigues Silva
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Os artigos publicados na International Journal of Health and Surgical Research são licenciados sob a Creative Commons Attribution 4.0 International (CC BY 4.0).
Isso permite que outros distribuam, remixem, adaptem e criem a partir do trabalho publicado, para qualquer finalidade, incluindo comercial, desde que seja dado o devido crédito ao autor original e à revista.
Os autores mantêm os direitos autorais de seus trabalhos e concedem à revista o direito de primeira publicação.
