P0323REVERSIBLE RENAL FUNCTION DECLINE ASSOCIATED WITH NIRAPARIB

Abstract

Abstract Background and Aims Inhibitors of poly-ADP-ribose-polymerase-1 (PARP) are prescribed for the treatment of metastatic breast and ovarian cancers. Clinical data trials suggest that niraparib may not have adverse effects on the kidney. Method We present a descriptive case series of renal function parameters of all the patients who received niraparib for maintenance treatment of recurrent ovarian cancer in a tertiary care center. Twenty patients received niraparib for the first time between april 2018 and march 2019 in the Georges Pompidou European Hospital, Paris, France. Four patients were excluded from the analysis because of lack of repeated serum creatinine (Scr) measurements during the first 4 months following niraparib introduction. Results The patients ranged in age from 51 to 82 years. All patients were women with high grade serous ovarian carcinoma. Personal medical history of hypertension was present in 68% and diabetes in 18% of patients. All patients received carboplatin and 90% received bevacizumab as maintenance treatment after first-line chemotherapy. Niraparib was introduced on average 3 years (range 2 to 9 years) after the diagnosis of cancer, at a dosage of 200 mg/day in all patients. The median Scr at baseline was 84 μmol/l (range 62 to 114 µmol/l). All patients experienced an increase in Scr level over the 3 months following niraparib introduction. The average max Scr increase was 1.35 times baseline (median Scr 117µmol/l, range 88 to 155 µmol/l, p<0.0001 compared to baseline values), and 3 patients (18%) developed stage 1 KDIGO Acute Kidney Injury/Disease (Scr increase > 1.5-2 fold baseline). None of the cases had biochemical signs of tubular or glomerular injury. Urinary creatinine clearance was higher than urinary clearance of 51Cr-EDTA, making interaction with tubular creatinine secretion unlikely. Kidney biopsy was performed in one patient who developed albuminuria. Microscopic examination identified mild tubular atrophy and interstitial fibrosis without inflammatory lesion Immunofluorescence analysis did not show immune deposits. Mesangiolysis was found in some glomeruli, typical of bevacizumab effects. Niraparib was interrupted in all but 1 patient (95%), because of haematological toxicity (n=7), tumoral progression (n=7) or gastro-intestinal toxicity (n=1). Average Scr level returned to baseline (82 µmol/l, range 62 to 107 µmol/l) over the 2 months following discontinuation. Conclusion Niraparib is associated with a systematic and significant increase in Scr (+35%) without obvious sign of tubular or glomerular injury. Renal dysfunction is mainly reversible after discontinuation. Decline of renal function under treatment may not be an incentive to stop treatment automatically. Physicians prescribing this agent should be aware of this complication.