Recent eUpdate to the ESMO Clinical Practice Guidelines on renal cell carcinoma on cabozantinib and nivolumab for first-line clear cell renal cancer

This eUpdate outlines updated treatment recommendations for first-line advanced clear cell renal cancer (Figure 1).1Escudier B. Porta C. Schmidinger M. et al.Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2019; 30: 706-720Abstract Full Text Full Text PDF PubMed Scopus (320) Google Scholar The changes are based on recent data for the combination of cabozantinib and nivolumab, which is now recommended as front-line therapy for advanced disease [I, A].2Choueiri T.K. Powles T. Burotto M. et al.696O_PR Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial.Ann Oncol. 2020; 31 (abstr S1159)PubMed Google Scholar This is based on data from the CheckMate 9ER study, which is one of a number of practice-changing studies comparing programmed cell death protein 1 (PD-1) inhibitors plus vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs) versus sunitinib in the front-line setting.3Rini B.I. Plimack E.R. Stus V. et al.Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.N Engl J Med. 2019; 380: 1116-1127Crossref PubMed Scopus (1189) Google Scholar,4Motzer R.J. Rini B.I. McDermott D.F. et al.Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial.Lancet Oncol. 2019; 20: 1370-1385Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar Results showed that the study met the primary endpoint of progression-free survival, with a median of 16.6 months for the combination versus 8.3 months for sunitinib (P < 0.0001). There was also a significant overall survival advantage for cabozantinib and nivolumab at interim analysis (18.1 months median follow-up) [hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.40-0.89; P < 0.001]. Reponses rates also significantly favoured the combination (56% versus 27% and HR 0.51, 95% CI 0.41-0.64, respectively). These benefits appeared to be irrespective of International Metastatic Database Consortium (IMDC) prognostic subgroups and programmed death-ligand 1 (PD-L1) biomarker status. No new adverse event (AE) signals were identified and AE profiles were in line with expectation. A large proportion of patients (56%) had dose reductions of cabozantinib from 40 mg to 20 mg. Quality-of-life data favoured the cabozantinib and nivolumab combination. Cross-trial comparisons between these front-line combination trials, such as axitinib/pembrolizumab or ipilimumab/nivolumab, are not advised.2Choueiri T.K. Powles T. Burotto M. et al.696O_PR Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial.Ann Oncol. 2020; 31 (abstr S1159)PubMed Google Scholar, 3Rini B.I. Plimack E.R. Stus V. et al.Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.N Engl J Med. 2019; 380: 1116-1127Crossref PubMed Scopus (1189) Google Scholar, 4Motzer R.J. Rini B.I. McDermott D.F. et al.Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial.Lancet Oncol. 2019; 20: 1370-1385Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar The recommendations for these other combinations have not changed from the previous eUpdate. •The combination of cabozantinib and nivolumab is now recommended as front-line therapy for advanced disease [I, A]. No external funding has been received. Production costs have been covered by ESMO from central funds.