Summary
The treatment landscape of advanced and metastatic renal cell carcinoma (RCC) has changed fundamentally over the last two decades with the introduction of tyrosine kinase inhibitors (TKIs) in 2005 and immune checkpoint inhibitors (ICIs) about 10 years later, both demonstrating significantly improved overall survival (OS) rates across all RCC risk categories. Currently, combination therapies represent the standard-of-care in the first-line setting of clear cell RCC in almost all cases. In this short review article, the most recent therapeutic advances in early and advanced stage of clear cell RCC are summarized.
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References
Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385:683–94.
Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab as post nephrectomy adjuvant therapy for patients with renal cell carcinoma: Results from 30-month follow-up of KEYNOTE-564. J Clin Oncol. 2022;40(6_suppl):290.
Motzer RJ, Russo P, Guenwald V, et al. Adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy: Results from the randomized, phase III CheckMate 914 trial. Ann Oncol. 2022;33(7_suppl):S808–S69.
Bex A, Uzzo R, Karam JA, Master VA, et al. IMmotion010: Efficacy and safety from the phase III study of atezolizumab (atezo) vs placebo (pbo) as adjuvant therapy in patients with renal cell carcinoma (RCC) at increased risk of recurrence after resection. Ann Oncol. 2022;33(7_suppl):S808–S69.
Allaf M, Kim SE, Harshman LC, McDermott DF, et al. Phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients (Pts) with renal cell carcinoma (RCC) undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143), a National Clinical Trials Network trial. Ann Oncol. 2022;33(7_suppl):S808–S69.
Powels T, Albiges L, Bex A, et al. ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma. Ann Oncol. 2021;32(12):1511–9.
Motzer RJ, Tannir NM, McDermott DF, et al. Conditional survival and 5‑year follow-up in CheckMate 214: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in advanced renal cell carcinoma (aRCC). Ann Oncol. 2021;32(suppl_5):S678.
Tannir NM, Signoretti S, Choueiri TK, et al. Efficacy and safety of nivolumab plus ipilimumab (N+I) versus sunitinib (S) for first-line treatment of patients with advanced sarcomatoid renal cell carcinoma (sRCC) in the phase 3 CheckMate 214 trial with extended 5‑year minimum follow-up. J Clin Oncol. 2022;40(6_suppl):352.
Rini BL, Plimack ER, Stus V, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426. J Clin Oncol. 2021;39(15_suppl):4500.
Powels T, Choueiri TK, Burotto M, Escudier B, et al. Final overall survival analysis and organ-specific target lesion assessments with two-year follow-up in CheckMate 9ER: Nivolumab plus cabozantinib versus sunitinib for patients with advanced renal cell carcinoma. J Clin Oncol. 2022;40(6_suppl):350.
Motzer R, Alekseev B, Rha SY, Porta C, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289–300.
Choueiri TK, Powels TB, Albiges L, Burotto M, et al. Phase III study of cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC) of IMDC intermediate or poor risk (COSMIC-313). Ann Oncol. 2022;33(7_suppl):S808–S69.
Recio-Boiles A, et al. Network meta-analysis (NMA) of second-line (2L) treatment options in metastatic renal cell carcinoma. J Clin Oncol. 2022;40(6_suppl):337.
Motzer RJ, Hutson TE, Glen H, Michaelson MD, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015;16(15):1473–82.
Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med. 2005;353(23):2477–90.
Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, et al. Belzutifan for renal cell carcinoma in von Hippel-Lindau disease. N Engl J Med. 2021;385(22):2036–46.
Bauer TM, Chouieri TK, Papadopoulos KP, et al. The oral HIF‑2 α inhibitor MK-6482 in patients with advanced clear cell renal cell carcinoma: updated follow-up of a phase I/II study. J Clin Oncol. 2021;39(6_suppl):273.
Choueiri TK, Albiges L, Fan L, Perini RF, et al. Phase III study of the hypoxia-inducible factor 2α (HIF-2α) inhibitor MK-6482 versus everolimus in previously treated patients with advanced clear cell renal cell carcinoma (ccRCC). J Clin Oncol. 2020;38(15_suppl):TPS5094.
Calvo E, Boni V, Chaudhry A, Debruyne PR, et al. Nemvaleukin alfa in patients with advanced renal cell carcinoma: ARTISTRY‑1. J Clin Oncol. 2022;40(6_suppl):330.
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Published first in JATROS Hämatologie & Onkologie, Ausgabe 5/22.
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Mühlmann, J. Update on systemic therapy for clear cell renal cell carcinoma. memo 16, 38–41 (2023). https://doi.org/10.1007/s12254-022-00867-w
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DOI: https://doi.org/10.1007/s12254-022-00867-w