Urol. praxi. 2024;25(1):32-37 | DOI: 10.36290/uro.2024.015

Management of treatment-related adverse effects in renal cell carcinoma

MUDr. Martin Matějů, Ph.D., MUDr. Michal Zubaľ
Onkologická klinika Všeobecné fakultní nemocnice v Praze a 1. lékařské fakulty, Praha

The paradigm of treatment of metastatic clear cell renal carcinoma (mccRCC) has repeatedly undergone significant changes in recent decades - from treatment with cytokines, interleukin-2 and interferon-α to therapy with tyrosine kinase inhibitors (TKIs) or mammalian target of rapamycin (mTOR) inhibitors to combined regimens based on immune checkpoint inhibitors (ICI). The combinations of ICI+ICI or ICI+TKIs have been fully established in the first line of therapy of mRCC in the past decade, based on large phase III studies using sunitinib as a comparator. These include CheckMate214 (ipilimumab plus nivolumab), KEYNOTE 426 (pembrolizumab plus axitinib), JAVELIN Renal 101 (avelumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib) and CLEAR (pembrolizumab plus lenvatinib) study. Thanks to results of the above-mentioned studies there has been a significant expansion of the armamentarium of available treatment options, especially in the first line of mccRCC palliative therapy, and thus a remarkable shift in the approach to RCC therapy in general. Almost unusual agreement in this regard can be perceived in both international and national clinical guidelines. At present, Czech clinicians can choose from various combinations of the aforementioned agents. It can be assumed that in the future the range of treatment reimbursed by public health insurance will continue to expand. The indication of first-line therapy which plays a crucial role in RCC treatment algorithm will then require to carefully assess various clinical factors, economic aspects and, last but not least, the adverse events profile of each combination and, in accordance with the principles of personalized medicine, consider the optimal treatment for each individual patient. With regard to clinical practice in urology, this article strives to briefly describe the safety profiles and adverse events of individual drugs and their combinations used currently in the treatment of RCC and to outline possible therapeutic approaches to these adverse events.

Keywords: adverse events, checkpoint inhibitors, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, kidney cancer.

Accepted: February 28, 2024; Published: March 15, 2024  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Matějů M, Zubaľ M. Management of treatment-related adverse effects in renal cell carcinoma. Urol. praxi. 2024;25(1):32-37. doi: 10.36290/uro.2024.015.
Download citation

References

  1. Motzer RJ, Hutson TE, Tomczak P, et al. Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma. Journal of Clinical Oncology. 2009;27(22):3584-3590. Go to original source... Go to PubMed...
  2. Alonso-Gordoa T, García-Bermejo ML, Grande E, et al. Targeting Tyrosine kinases in Renal Cell Carcinoma: "New Bullets against Old Guys". International Journal of Molecular Sciences. 2019;20(8):1901. Go to original source... Go to PubMed...
  3. Heng DYC, Xie W, Regan MM, et al. Prognostic Factors for Overall Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor - Targeted Agents: Results From a Large, Multicenter Study. Journal of Clinical Oncology. 2009;27(34):5794-5799. Go to original source... Go to PubMed...
  4. Haanen JBAG, Larkin J, Choueiri TK, et al. Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma. ESMO Open. 2023;8(3):101210. Go to original source... Go to PubMed...
  5. SÚKL, Detail varianty léčivého přípravku (YERVOY - 5MG/ML INF CNC SOL 1X10ML) [Internet] [Available from: https://prehledy.sukl.cz/prehled_leciv.html#/leciva/0185101.
  6. Choueiri TK, Eto M, Motzer R, et al. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study. The Lancet Oncology. 2023;24(3):228-238. Go to original source... Go to PubMed...
  7. Pal SK, Albiges L, Tomczak P, et al. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multi­centre, randomised, open-label, phase 3 trial. Lancet. 2023;402(10397):185-195. Go to original source... Go to PubMed...
  8. Hallare J, Gerriets V. Half Life. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023.
  9. EMA, Sutent, Inlyta, Votrient, Cabometyx, Kisplyx : EPAR - Product information [Internet] [Available from: https://www.ema.europa.eu/en/medicines/human.
  10. EMA, Afinitor : EPAR - Product information [Internet] Availab­le from: https://www.ema.europa.eu/en/medicines/human/EPAR/afinitor#product-information-section.
  11. Motzer RJ, Escudier B, Oudard S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma. Cancer. 2010;116(18):4256-4265. Go to original source... Go to PubMed...
  12. NCCN Guidelines, Kidney Cancer, Version: 1.2024, [Internet].
  13. Dutcher JP, Flippot R, Fallah J, Escudier B. On the Shoulders of Giants: The Evolution of Renal Cell Carcinoma Treatment - Cytokines, Targeted Therapy, and Immunotherapy. American Society of Clinical Oncology Educational Book. 2020(40):418-435. Go to original source... Go to PubMed...
  14. Kyllarová A, Kubeček O, Trojanová P, et al. Immunotherapy related toxicities. Onkologie. 2017;11:83-87. Go to original source...
  15. Lakomý R, Poprach A. Sideeffects of Modern Immunotherapy and How to Solve Them in the Clinics. Klin Onkol. 2015;28 Suppl 4:4s103-114. Go to original source...
  16. Motzer RJ, Escudier B, George S, et al. Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer. 2020;126(18):4156-4167. Go to original source... Go to PubMed...
  17. Powles T, Tomczak P, Park SH, et al. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2022;23(9):1133-1144. Go to original source... Go to PubMed...
  18. Albiges L, Tannir NM, Burotto M, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020;5(6):e001079. Go to original source... Go to PubMed...
  19. Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. The Lancet Oncology. 2020;21(12):1563-1573. Go to original source... Go to PubMed...
  20. Motzer RJ, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial. The Lancet Oncology. 2022;23(7):888-898. Go to original source... Go to PubMed...
  21. Grünwald V, Voss MH, Rini BI, et al. Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. British journal of cancer. 2020;123(6):898-904. Go to original source... Go to PubMed...
  22. Choueiri TK, Powles T, Albiges L, et al. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. New England Journal of Medicine. 2023;388(19):1767-1778. Go to original source... Go to PubMed...
  23. Choueiri TK, Plimack ER, Powles T, et al. Phase 3 study of first-line treatment with pembrolizumab + belzutifan + lenvatinib or pembrolizumab/quavonlimab + lenvatinib versus pembrolizumab + lenvatinib for advanced renal cell carcinoma (RCC). Journal of Clinical Oncology. 2022;40(6_suppl):TPS399-TPS. Go to original source...
  24. Choueiri TK, Mcdermott DF, Merchan J, et al. Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. The Lancet Oncology. 2023;24(5):553-562. Go to original source... Go to PubMed...
  25. Conroy M, Naidoo J. Immune-related adverse events and the balancing act of immunotherapy. Nature Communications. 2022;13(1). Go to original source... Go to PubMed...




Urology for Practice

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.