Safety and tolerability of cabozantinib in renal cancer and hepatocarcinoma
DOI:
https://doi.org/10.30827/ars.v64i1.26725Keywords:
Cabozantinib, Carcinoma, Renal Cell, Drug-Related Side Effects and Adverse Reactions, Carcinoma, HepatocellularAbstract
Introduction: Cabozantinib is a drug indicated for the treatment of renal cancer and hepatocarcinoma with proven efficacy in clinical trials. However, when we analyze its safety profile, the pivotal trials themselves show a high percentage of adverse effects, making it necessary in many cases to reduce the dose or interrupt treatment due to toxicity. Therefore, our study aims to analyze the tolerability and safety of cabozantinib in our population.
Method: Observational, retrospective and single-center study. Different variables related to the safety and tolerability of the drug were evaluated. To assess toxicity, the National Cancer Institute criteria (CTCAE version 5.0) were used. Tolerance was assessed based on the presence of adverse effects during treatment with cabozantinib. A descriptive and inferential statistical analysis of the data was performed.
Results: A total of 17 patients were included (mean age: 63.5 years old). All of them presented adverse effects. The main toxicities presented of any grade were asthenia, diarrhea, skin toxicity, hypomagnesemia, hypertransaminemia, and palmoplantar syndrome. 41.2% were grade 3 toxicity, the main adverse reactions being hypertransaminemia and hypomagnesemia. Hospital admission due to drug toxicity was required by 23.5%. Dose reduction to 40 mg due to toxicity was required by 94.1% of patients.
Conclusions: Cabozantinib has an unfavorable safety profile with a high percentage of adverse effects that require dose reduction or treatment interruption.
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References
Agencia Española de Medicamentos y Productos Sanitarios [Internet]. Ficha técnica de Cabometyx 20 mg comprimidos recubiertos con película; [citado 26 de febrero de 2022]. Disponible en: https://cima.aemps.es/cima/dochtml/ft/1161136002/FT_1161136002.html
Gordan JD, Kennedy EB, Abou-Alfa GK, Beg MS, Brower ST, Gade TP, et al. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline. J Clin Oncol. 2020; 38(36):4317-4345. doi: 10.1200/JCO.20.02672
Vogel A, Cervantes A, Chau I, Daniele B, Llovet JM, Meyer T, et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4):iv238–55. doi: 10.1093/annonc/mdy308
Vogel A, Martinelli E, ESMO Guidelines Committee. Updated treatment recommendations for hepatocellular carcinoma (HCC) from the ESMO Clinical Practice Guidelines. Ann Oncol. 2021; 32(6):801–5. doi: 10.1016/j.annonc.2021.02.014
Ministerio de Sanidad [Internet]. BIFIMED: Buscador de la Información sobre la situación de financiación de los medicamentos [citado 14 de noviembre de 2022]. Disponible en: https://www.sanidad.gob.es/profesionales/medicamentos.do?metodo=verDetalle&cn=713744
National Comprehensive Cancer Network (NCCN) [Internet]. NCCN Clinical Practice Guidelines in Oncology - Kidney Cancer. Version 4.2022. [citado 28 de febrero de 2022]. Disponible en: https://www.nccn.org/guidelines/guidelines-detail
Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019; 30(5):706–20. doi: 10.1093/annonc/mdz056
Tenold M, Ravi P, Kumar M, Bowman A, Hammers H, Choueiri TK, et al. Current Approaches to the Treatment of Advanced or Metastatic Renal Cell Carcinoma. Am Soc Clin Oncol Educ Book. 2020; 40:1–10. doi: 10.1200/EDBK_279881
Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018; 379(1):54–63. doi: 10.1056/NEJMoa1717002
Choueiri TK, Halabi S, Sanford BL, Hahn O, Michaelson MD, Walsh MK, et al. Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. J Clin Oncol. 2017; 35(6):591–7. doi: 10.1200/JCO.2016.70.7398
Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021; 384(9):829-841. doi:10.1056/NEJMoa2026982
Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016; 17(7):917–27. doi: 10.1016/S1470-2045(16)30107-3
Choueiri TK, Escudier B, Powles T, Mainwaring P, Rini BI, Donskov F, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma. N Engl J Med. 2015; 373(19):1814–23. doi: 10.1056/NEJMoa1510016
Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021; 384(9):829-841. doi: 10.1056/NEJMoa2026982
Tovoli F, Dadduzio V, De Lorenzo S, Rimassa L, Masi G, Iavarone M, et al. Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma. Liver Cancer. 2021; 10(4):370–9. doi: 10.1159/000515551
Finkelmeier F, Scheiner B, Leyh C, Best J, Fründt TW, Czauderna C, et al. Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort. Liver Cancer. 2021; 10(4):360–9. doi: 10.1159/000515490
Prisciandaro M, Ratta R, Massari F, Fornarini G, Caponnetto S, Iacovelli R, et al. Safety and Efficacy of Cabozantinib for Metastatic Nonclear Renal Cell Carcinoma: Real-world Data From an Italian Managed Access Program. Am J Clin Oncol. 2019; 42(1):42–5. doi: 10.1097/COC.0000000000000478
Bodnar L, Kopczyńska A, Żołnierek J, Wieczorek-Rutkowska M, Chrom P, Tomczak P. Real-world Experience of Cabozantinib as Second- or Subsequent Line Treatment in Patients With Metastatic Renal Cell Carcinoma: Data From the Polish Managed Access Program. Clin Genitourin Cancer. 2019; 17(3):e556–64. doi: 10.1016/j.clgc.2019.02.002
McElwee JH, Gourdin TS, Mikoll J, Weeda E, Sion AM. Cabozantinib use in metastatic renal cell carcinoma patients in clinical practice: Evaluation of dosing patterns, tolerability, and outcomes compared to clinical trials. J Oncol Pharm Pract. 2020; 26(4):861–5. doi: 10.1177/1078155219875509
Peverelli G, Raimondi A, Ratta R, Verzoni E, Bregni M, Cortesi E, et al. Cabozantinib in Renal Cell Carcinoma With Brain Metastases: Safety and Efficacy in a Real-World Population. Clin Genitourin Cancer. 2019; 17(4):291–8. doi: 10.1016/j.clgc.2019.05.002
Pérez-Ricart A, Gea-Rodríguez E, Roca-Montañana A, Gil-Máñez E, Pérez-Feliu A, Pérez-Ricart A, et al. Integración de la farmacovigilancia en la rutina del servicio de farmacia: nueve años de experiencia. Farmacia Hospitalaria. 2019; 43(4):128–33. doi: 10.7399/fh.11169
Aagaard L, Hansen EH. Side effects of antineoplastic and immunomodulating medications reported by European consumers. J Res Pharm Pract. 2013; 2(1):44. doi: 10.4103/2279-042X.114091
Martino GG, Rojas GJ, Sánchez de Paz MP, Isa S, Bres Bullrich M, Camino MV, et al. Seguridad de fármacos antineoplásicos e inmunomoduladores aplicados a la neurología. Neurol Argentina. 2019;11(3):136–44. doi: 10.1016/j.neuarg.2019.03.001
Schmidinger M, Danesi R. Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma. Oncologist. 2018; 23(3):306–15. doi: 10.1634/theoncologist.2017-0335
Gan CL, Dudani S, Wells JC, Donskov F, Pal SK, Dizman N, et al. Cabozantinib real-world effectiveness in the first-through fourth-line settings for the treatment of metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. Cancer Medicine. 2021; 10(4):1212–21. doi: 10.1002/cam4.3717
Albiges L, Fléchon A, Chevreau C, Topart D, Gravis G, Oudard S, et al. Real-world evidence of cabozantinib in patients with metastatic renal cell carcinoma: Results from the CABOREAL Early Access Program. Eur J Cancer. 2021; 142:102–11. doi: 10.1016/j.ejca.2020.09.030
Martini DJ, Evans ST, Liu Y, Shabto JM, Uner OE, Olsen TA, et al. Analysis of Toxicity and Clinical Outcomes in Full Versus Reduced Starting Dose Cabozantinib in Metastatic Renal Cell Carcinoma Patients. Clin Genitourin Cancer. 2022; 20(1):53–9. doi: 10.1016/j.clgc.2021.11.004
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