Abstract
PurposeOlaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for ovarian and metastatic breast cancer. Increased serum creatinine levels have been observed in patients taking olaparib, but the underlying mechanism is unknown. This study aimed to investigate if patients receiving olaparib have increased creatinine levels during olaparib treatment and whether this actually relates to a declined glomerular filtration rate (GFR).MethodsWe retrospectively identified patients using olaparib at the Netherlands Cancer Institute – Antoni van Leeuwenhoek (NKI-AVL) from 2012 until 2020. Patients with at least one plasma or serum sample available at baseline/off treatment and during olaparib treatment were included. Cystatin C levels were measured, creatinine levels were available and renal function was determined by calculating the estimated glomerular filtration rate (eGFR) using the Creatinine Equation (CKD-EPI 2009) and the Cystatin C Equation (CKD-EPI 2012).ResultsIn total, 66 patients were included. Olaparib treatment was associated with a 14% increase in median creatinine from 72 (inter quartile range (IQR): 22) μmol/L before/off treatment to 82 (IQR: 20) μmol/L during treatment (p < 0.001) and a 13% decrease in median creatinine-derived eGFR from 86 (IQR: 26) mL/min/1.73 m2 before/off treatment to 75 (IQR: 29) mL/min/1.73 m2 during treatment (p < 0.001). Olaparib treatment had no significant effect on median cystatin C levels (p = 0.520) and the median cystatin C–derived eGFR (p = 0.918).ConclusionsThis study demonstrates that olaparib likely causes inhibition of renal transporters leading to a reversible and dose-dependent increase in creatinine and does not affect GFR, since the median cystatin C–derived eGFR was comparable before/off treatment and during treatment of olaparib. Using the creatinine-derived eGFR can give an underestimation of GFR in patients taking olaparib. Therefore, an alternative renal marker such as cystatin C should be used to accurately calculate eGFR in patients taking olaparib.
Highlights
Olaparib is a potent poly (ADP-ribose) polymerase (PARP) inhibitor approved for the treatment of patients with ovarian cancer and patients with breast cancer (BRCA)–mutated human epidermal growth factor receptor-2 (HER2) negative metastatic breast cancer [1, 2]
One patient had an impaired renal function at baseline and, received an a priori dose reduction to 200 mg BID
Baseline estimated glomerular filtration rate (eGFR) values calculated with creatinine and cystatin C were similar
Summary
Olaparib is a potent poly (ADP-ribose) polymerase (PARP) inhibitor approved for the treatment of patients with ovarian cancer and patients with breast cancer (BRCA)–mutated human epidermal growth factor receptor-2 (HER2) negative metastatic breast cancer [1, 2]. Olaparib is orally administrated at a recommended dose of 300 mg (tablets) or 400 mg (capsules) twice a day (BID). In patients taking the recommended dose, increased serum creatinine levels (up to 23%) over baseline were observed [2]. Creatinine is an endogenous product of creatine metabolism in muscles and is used as a marker to calculate the glomerular filtration rate (GFR). The GFR is used as a functional parameter to evaluate renal function of patients in clinical practice. Creatinine is primarily filtered by the glomerulus, but active tubular secretion accounts
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