A Matching-Adjusted Indirect Comparison of Nivolumab Plus Cabozantinib Versus Pembrolizumab Plus Axitinib in Patients with Advanced Renal Cell Carcinoma

European Urology Oncology, 2023


The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials.


To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib.

Design, setting, and participants

Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426.


Nivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially).

Outcome measurements and statistical analysis

Hazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib.

Results and limitations

After balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53-0.93]; p = 0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms: HR [95% CI] 0.48 [0.34-0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67-1.44]; p = 0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [-1.7 to 18.4]; p = 0.10) and longer duration of response (HR [95% CI] 0.79 [0.47-1.31]; p = 0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted.


Nivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC.

View abstract


McGregor B, Geynisman DM, Burotto M, Suárez C, Bourlon MT, Barata PC, Gulati S, Huo S, Ejzykowicz F, Blum SI, Tejo VD, Hamilton M, May JR, Du EX, Wu A, Kral P, Ivanescu C, Chin A, Betts KA, Lee CH, Choueiri TK, Cella D, Porta C