When starting treatment with everolimus in elderly cancer patients (pts), clinicians are often concerned about everolimus related toxicity. Elderly pts frequently have comorbidities and are considered more fragile. Therefore, upfront dose reduction of everolimus to prevent toxicity is applied more readily in elderly pts. However, very limited data are available on the pharmacokinetics (PK) in elderly pts and therefore, the influence of age on everolimus PK in cancer pts is yet unknown. The objective of this study was to determine the effect of age on everolimus PK.
In two PK studies in pts with either metastatic breast cancer or advanced thyroid cancer treated with everolimus 10mg OD, everolimus PK was compared between elderly pts (age ≥ 70 years ) and control pts (age
19 elderly and 56 control pts were included. Comparative PK data are shown in table 1. Everolimus exposure in both whole blood and plasma did not differ significantly between the two groups. Dose reductions or discontinuations due to toxicity occurred in 42% of elderly and 40% of control pts (p = .73). Table: results.
|Parameter||Control (n = 56); mean (range; SD)||Elderly (n = 19); mean (range; SD)||P|
|Age (years)||57.5 (37-69)||73.4 (70-80)|
|Whole blood AUC0-24||580.0 (223.1)||507.9 (182.3)||.208|
|Plasma AUC0-24||209.1 (79.3)||190.0 (66.3)||.349|
AUC0–24 = area under concentration–time curve from zero to 24 hours, µg*h/L
Everolimus PK is not affected by older age. Upfront dose adjustment, such as frequently considered in elderly pts, is not supported by PK and clinical data and needs to be reconsidered.
Clinical trial identification
NCT01948960 AND NCT01118065
Legal entity responsible for the study
Radboud University Medical Center
All authors have declared no conflicts of interest.