Cabozantinib ( Cabometyx ) has improved progression-free survival ( PFS ), overall survival ( OS ) and objective response rate ( ORR ) compared with Everolimus in patients with advanced renal cell carcinoma ( RCC ) after prior antiangiogenic therapy in the phase III METEOR trial.
Limited data are available on the use of targeted therapies in older patients with advanced renal cell carcinoma.
Efficacy and safety in METEOR were retrospectively analysed for three age subgroups: less than 65 ( n = 394 ), 65–74 ( n = 201 ) and greater than or equlal to 75 years ( n = 63 ).
The progression-free survival, overall survival and objective response rate were improved with Cabozantinib compared with Everolimus in all age subgroups.
The PFS hazard ratios ( HRs ) were 0.53 ( 95% confidence interval [ CI ]: 0.41–0.68 ), 0.53 ( 95% CI: 0.37–0.77 ) and 0.38 ( 95% CI: 0.18–0.79 ) for less than 65, 65–74 and greater than or equal to75 years, respectively, and the OS hazard ratios were 0.72 ( 95% CI: 0.54–0.95 ), 0.66 ( 95% CI: 0.44–0.99 ) and 0.57 ( 95% CI: 0.28–1.14 ).
The objective response rate for Cabozantinib versus Everolimus was 15% vs 5%, 21% vs 2% and 19% vs 0%, respectively.
No significant differences were observed in progression-free survival or overall survival with age as a categorical or continuous variable.
Grade III/IV adverse events were generally consistent across subgroups, although fatigue, hypertension and hyponatraemia occurred more frequently in older patients treated with Cabozantinib.
Dose reductions to manage adverse effects were more frequent in patients receiving Cabozantinib than in those receiving Everolimus.
Dose reductions and treatment discontinuation due to adverse effects were more frequent in older patients in both treatment groups.
In conclusion, Cabozantinib has improved progression-free survival, overall survival and objective response rate compared with Everolimus in previously treated patients with advanced renal cell carcinoma, irrespective of age group, supporting use in all age categories.
Proactive dose modification and supportive care may help to mitigate adverse effects in older patients while maintaining efficacy. ( Xagena )
Donskov F et al, Eur J Cancer 2020; 126: 1–10