Association Of Niraparib With Acute Kidney Injury In Patients With Ovarian Cancer

Abstract

Introduction/Background Poly (ADP-ribose) polymerase inhibitors are approved as maintenance therapy in ovarian cancer. Renal dysfunction is reported infrequently with niraparib within clinical trials. We sought to investigate this in a non-trial patient population. Methodology We retrospectively reviewed medical charts of all patients with ovarian cancer who received niraparib between October 2018 and September 2023 at our institution. Serum creatinine (SCr), blood pressure, and clinical review were recorded as per local guidelines (weekly in the first month, two weekly in the second month, monthly thereafter). Primary outcome was acute kidney injury (AKI) as per KDIGO criteria (>=50% rise in SCr) and 30-49% rise in baseline SCr (cut-off based on physiological variation). Results 77 patients were included for analysis. Median age 68 years (range 46-91). Baseline medical conditions: 32(41.6%) hypertension, 13(16.9%) diabetes, 7(9.1%) chronic kidney disease stage >=3, and 2(2.6%) arterial vascular disease. Pre-existing medications included 15(19.5%) renin-angiotensin-aldosterone-system inhibitors, 2(2.6%) NSAIDs, 3(3.9%) diuretics, and 1(1.3%) mineralocorticoid inhibitors. 48(75.3%) received niraparib in first-line setting whilst 29(37.7%) in the relapsed setting. 70(90.9%) received >=6 cycles of carboplatin-based chemotherapy and 14(18.2%) received prior bevacizumab. Starting dose of niraparib was 200mg in 70(90.9%) patients and 300mg in the remainder. Within 12 weeks of niraparib initiation, 35(45.5%) patients had a 30-49% increase in SCr whilst 22(28.6%) developed stage 1 AKI. There were no stage 2-3 AKIs. Concurrent AEs were common: 36(46%) hematological, 16(20.8%) hypertension, and 8(10.4%) gastrointestinal. On multivariate analysis, older age was significantly associated with AKI (HR 3.86, 95%CI 1.12-13.3; p=0.033). Concurrent hypertension was associated with 30-49% SCr rise (HR 3.18; 95%CI 1.09-9.29; p=0.035). Renal dysfunction was not associated with hypovolaemia or nephrotoxic medications. Conclusion AKI and mild SCr rise are common with niraparib independent of other factors besides older age and hypertension respectively. Further research into this mechanism is warranted along with proactive management of comorbidities. Disclosures REM received grants from GSK and MSD; honoraria from MSD, GSK, AstraZeneca, Ellipses, Shionogi, Clovis Oncology, Abbvie, Pharma&, and GI Innovation; and speaker fees from GSK, AstraZeneca, Eisai, Pharma&, MSD, and Clovis Oncology. All other authors disclose no conflicts of interest. Multivariate analysis of risk factors for developing AKI (SCr =50% from baseline) or mild SCr rise (SCr 30-49% from baseline) with niraparib.