ArticlePharmaceuticals (Basel, Switzerland)2021
Association between Olaparib Exposure and Early Toxicity in BRCA-Mutated Ovarian Cancer Patients: Results from a Retrospective Multicenter Study.
Article in Pharmaceuticals (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Therapeutic Drug Monitoring and Model-Informed Precision Dosing of Oral TKIs and PARP Inhibitors: A Practical Framework for Clinical Implementation.Clinical pharmacokinetics · 2026Review
- Article
- Cytochrome P450 inhibitor/inducer treatment patterns among patients in the United States with advanced ovarian cancer who were prescribed or were eligible for poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors in the first-line maintenance setting.Gynecologic oncology reports · 2024Article
- Combination of Osimertinib and Olaparib Therapy to Treat Non-Small Cell Lung Cancer and High-Grade Serous Ovarian Carcinoma: A Case Report.Current oncology (Toronto, Ont.) · 2024Article
- Improving olaparib exposure to optimize adverse effects management.Therapeutic advances in medical oncology · 2024Article
- A retrospective analysis of haematological side effects of olaparib in excess-weight and normal BMI patients with ovarian cancer.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2024Article
- Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology.Clinical pharmacokinetics · 2023Review
- Physiologically-based pharmacokinetic modeling for optimal dosage prediction of olaparib when co-administered with CYP3A4 modulators and in patients with hepatic/renal impairment.Scientific reports · 2023Article
- SNRPD1 conveys prognostic value on breast cancer survival and is required for anthracycline sensitivity.BMC cancer · 2023Article
- Safety of bevacizumab and olaparib as frontline maintenance therapy in advanced ovarian cancer: expert review for clinical practice.Frontiers in oncology · 2023Review
- Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology.Clinical pharmacokinetics · 2022Review
- Age Is a Risk Factor for Olaparib Dose Modification and Discontinuation in Patients With Ovarian Cancer.Cancer diagnosis & prognosisArticle
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Factors associated with olaparib toxicity remain unknown in ovarian cancer patients. The large inter-individual variability in olaparib pharmacokinetics could contribute to the onset of early significant adverse events (SAE). We aimed to retrospectively analyze the pharmacokinetic/pharmacodynamic relationship for toxicity in ovarian cancer patients from "real life" data. The clinical endpoint was the onset of SAE (grade III/IV toxicity or dose reduction/discontinuation). Plasma olaparib concentration was assayed using liquid chromatography at any time over the dosing interval. Trough concentrations (CminPred) were estimated using a population pharmacokinetic model. The association between toxicity and clinical characteristics or CminPred was assessed by logistic regression and non-parametric statistical tests. Twenty-seven patients were included, among whom 13 (48%) experienced SAE during the first six months of treatment. Olaparib CminPred was the only covariate significantly associated with increased risk of SAE onset (odds ratio = 1.31, 95%CI = [1.10; 1.57], for each additional 1000 ng/mL). The ROC curve identified a threshold of CminPred = 2500 ng/mL for prediction of SAE onset (sensitivity/specificity 0.62 and 1.00, respectively). This study highlights a significant association between olaparib plasma exposure and SAE onset and identified the threshold of 2500 ng/mL trough concentration as potentially useful to guide dose adjustment in ovarian cancer patients.
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