eUpdate – Renal Cell Carcinoma Treatment Recommendations

Published: 30.11.2020. Authors: ESMO Guidelines Committee

Clinical Practice Guidelines

This update refers to the Renal Cell Carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Escudier B, Porta C, Schmidinger M et al. Ann Oncol 2019; 30(5): 706–720.

Section

This eUpdate outlines updated treatment recommendations for first-line clear cell renal cancer, as shown in Figure 1. 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].(1) 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. (2,3) Results showed a significant overall survival advantage (OS) 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 and progression-free survival (PFS) 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%) dose reduced cabozantinib from 40 mg to 20 mg. Quality-of-life (QoL) data favoured the cabozantinib and nivolumab combination. Cross trial comparisons between these front-line combination trials, such as axitinib/pembrolizumab or ipilimumab/nivolumab, is not advised. (1-3) The recommendations for these other combinations have not changed from the previous eUpdate.

Recommendation

The combination of cabozantinib and nivolumab is now recommended as frontline therapy for advanced disease [I, A].

Renal-Cell-Carcinoma-Nov-2020 — Figure 1. Systemic first-line treatment of clear cell renal cell carcinoma (ccRCC)
a. ESMO-MCBS scores for new therapies/indications approved by the EMA since 1 January 2016. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee.
b. Where recommended treatment not available or contraindicated.
ccRCC, clear cell renal cell carcinoma; EMA, European Medicines Agency; ESMO-MCBS, ESMO-Magnitude of Clinical Benefit Scale; MCBS, Magnitude of Clinical Benefit Scale.

Section

References

Choueiri TK, 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(suppl 4);abstr S1159.
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.
Motzer RJ, Rini BI, McDermott DF, 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(10):1370-1385.