Adjuvant ipilimumab and nivolumab in renal cell carcinoma: more questions than answers

Immune checkpoint inhibitors, such as pembrolizumab (a PD-1 inhibitor), nivolumab (a PD-1 inhibitor), and ipilimumab (a CTLA-4 inhibitor), are widely used in patients with clear cell renal cell carcinoma. 1 Powles 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: 1511-1519 Summary Full Text Full Text PDF PubMed Google Scholar Single-agent PD-1 inhibitors, such as pembrolizumab or nivolumab, have activity in advanced disease. 2 Motzer RJ Escudier B McDermott DF et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015; 373: 1803-1813 Crossref PubMed Scopus (4094) Google Scholar , 3 McDermott DF Lee JL Bjarnason GA et al. Open-label, single-arm phase II study of pembrolizumab monotherapy as first-line therapy in patients with advanced clear cell renal cell carcinoma. J Clin Oncol. 2021; 39: 1020-1028 Crossref PubMed Scopus (89) Google Scholar Adjuvant pembrolizumab significantly improved disease-free survival after nephrectomy for patients with high-risk renal cell carcinoma in the KEYNOTE-564 study, and also produced an immature trend towards better overall survival. 4 Choueiri TK Tomczak P Park SH et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021; 385: 683-694 Crossref PubMed Google Scholar Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomised, phase 3 trialAdjuvant therapy with nivolumab plus ipilimumab did not improve disease-free survival versus placebo in patients with localised renal cell carcinoma at high risk of recurrence after nephrectomy. Our study results do not support this regimen for the adjuvant treatment of renal cell carcinoma. Full-Text PDF