Sequencing checkpoint inhibitor therapy in renal cell carcinoma

Initial therapy in patients with advanced renal cell carcinoma includes drugs that inhibit immune checkpoints, thereby blocking the negative regulators of an antitumour immune response. Currently, this therapy includes a combination of a PD-1 inhibitor and either a second checkpoint inhibitor, an antibody against CTLA4, or one of several small molecule inhibitors of the VEGF receptor. These PD-1-based combination therapies have improved clinical outcomes including overall survival. 1 Motzer RJ McDermott DF Escudier B et al. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer. 2022; 128: 2085-2097 Crossref PubMed Scopus (61) Google Scholar , 2 Rini BI Plimack ER Stus V et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019; 380: 1116-1127 Crossref PubMed Scopus (1915) Google Scholar , 3 Choueiri TK Powles T Burotto M et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021; 384: 829-841 Crossref PubMed Scopus (681) Google Scholar , 4 Motzer R Alekseev B Rha S-Y et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021; 384: 1289-1300 Crossref PubMed Scopus (681) Google Scholar Although use of checkpoint inhibitor-based combination therapy has led to a subset of patients who have a durable response and disease control without the need for further systemic therapy, the majority of patients will progress and require additional treatment. 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 trialThe addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity. These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials. Full-Text PDF