4.4 Review

Clinical Pharmacokinetics and Pharmacodynamics of Rucaparib

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Article Oncology

Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors

Michelle L. Green et al.

Summary: The purpose of this study was to develop a population pharmacokinetics (PPK) model for the oral poly(ADP-ribose) polymerase inhibitor rucaparib. The PPK analysis was conducted using PK data from multiple clinical studies and identified factors that affect the clearance of rucaparib. The results showed that rucaparib PK is influenced by various factors, but for the majority of the population, these factors do not have a clinically significant impact on its treatment. Additionally, the study validates the accuracy of the model and compares it with other study results, demonstrating no clinically meaningful pharmacokinetic differences across different indications or sex.

CANCER CHEMOTHERAPY AND PHARMACOLOGY (2022)

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Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial

Rebecca Kristeleit et al.

Summary: In patients with BRCA1 or BRCA2 mutated ovarian carcinoma, rucaparib demonstrated better progression-free survival compared to chemotherapy. The results of this study support rucaparib as an alternative treatment option for patients with relapsed BRCA-mutated ovarian carcinoma.

LANCET ONCOLOGY (2022)

Review Oncology

Comparative Efficacy and Safety of PARP Inhibitors as Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

Yangchun Xu et al.

Summary: This meta-analysis showed that PARP inhibitor monotherapy as maintenance treatment is effective in improving PFS for patients with BRCA mutated ovarian cancer, HRD patients, and overall population. While rucaparib and niraparib had higher incidences of grade 3 or 4 adverse events compared to olaparib, treatment discontinuations were not significantly different between the three drugs. Overall, all three drugs were effective and presented manageable adverse events.

FRONTIERS IN ONCOLOGY (2021)

Article Oncology

Pharmacokinetics and safety of rucaparib in patients with advanced solid tumors and hepatic impairment

Nikolay Grechko et al.

Summary: Patients with moderate hepatic impairment showed mildly increased area under the concentration-time curve (AUC) for rucaparib compared to those with normal hepatic function. While more patients with moderate hepatic impairment experienced treatment-emergent adverse events, only a small proportion of these events were considered treatment-related.

CANCER CHEMOTHERAPY AND PHARMACOLOGY (2021)

Article Oncology

Population exposure-efficacy and exposure-safety analyses for rucaparib in patients with recurrent ovarian carcinoma from Study 10 and ARIEL2

Gottfried E. Konecny et al.

Summary: This study aimed to evaluate the correlations between rucaparib exposure and efficacy and safety endpoints in patients with recurrent ovarian carcinoma. Results showed that rucaparib exposure was positively correlated with efficacy and negatively correlated with safety.

GYNECOLOGIC ONCOLOGY (2021)

Review Biochemistry & Molecular Biology

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy

Giorgio Valabrega et al.

Summary: PARP inhibitors can interfere with the activity of PARP on DNA, thereby inhibiting single-strand DNA damage repair. Although these drugs share some similarities, they also have significant differences in terms of chemical structure and pharmacodynamics. These differences may contribute to the different safety profiles and activity of PARPi.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Oncology

Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

Hongmei Wang et al.

Summary: The study evaluated the clinical efficacy and safety of PARPi monotherapy maintenance treatment for platinum-sensitive ROC patients, finding that olaparib and niraparib had significant benefits for patients with gBRCA mutations, and all three PARPi treatments effectively prolonged PFS for patients with ROC.

FRONTIERS IN ONCOLOGY (2021)

Article Oncology

A phase 1, open-label, drug-drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors

Mingxiang Liao et al.

Summary: Rucaparib 600 mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. The safety profile of rucaparib when coadministered with rosuvastatin or oral contraceptives was consistent with rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary when coadministered with rucaparib.

CANCER CHEMOTHERAPY AND PHARMACOLOGY (2021)

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Acquired RAD51C Promoter Methylation Loss Causes PARP Inhibitor Resistance in High-Grade Serous Ovarian Carcinoma

Ksenija Nesic et al.

Summary: This study revealed that methylation patterns in the RAD51C promoter are closely associated with sensitivity to PARP inhibitors, with complete or heterogeneous methylation affecting drug resistance development. Additionally, genomic profiling showed that resistance to PARPi can be acquired independently in genetically distinct lineages.

CANCER RESEARCH (2021)

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Discrepancy in calculated and measured glomerular filtration rates in patients treated with PARP inhibitors

Graziela Zibetti Dal Molin et al.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER (2020)

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Exploring and comparing adverse events between PARP inhibitors

Christopher J. LaFargue et al.

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Article Pharmacology & Pharmacy

Pharmacokinetic Study of Rucaparib in Patients With Advanced Solid Tumors

Geoffrey Shapiro et al.

CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT (2019)

Review Oncology

PARP Inhibitors in Ovarian Cancer

Gloria Mittica et al.

RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY (2018)

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In vitro and in vivo assessment of the mechanism of action of the PARP inhibitor rucaparib

Liliane Robillard et al.

CANCER RESEARCH (2017)

Article Oncology

Poly (ADP-Ribose) Polymerase Inhibitors: Recent Advances and Future Development

Clare L. Scott et al.

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Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair

Raphael Ceccaldi et al.

NATURE (2015)

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Liquid chromatography-tandem mass spectrometric assay for the PARP inhibitor rucaparib in plasma

Rolf W. Sparidans et al.

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The role of PARP inhibitors in the treatment of gynecologic malignancies

Raquel E. Reinbolt et al.

FRONTIERS IN ONCOLOGY (2013)

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Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors

Elisabet Wahlberg et al.

NATURE BIOTECHNOLOGY (2012)

Review Biochemistry & Molecular Biology

Synthetic lethality: General principles, utility and detection using genetic screens in human cells

Sebastian M. B. Nijman

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ATM Deficiency Sensitizes Mantle Cell Lymphoma Cells to Poly(ADP-Ribose) Polymerase-1 Inhibitors

Chris T. Williamson et al.

MOLECULAR CANCER THERAPEUTICS (2010)

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PARP inhibition: PARP1 and beyond

Michele Rouleau et al.

NATURE REVIEWS CANCER (2010)

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Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors

Ana M. Mendes-Pereira et al.

EMBO MOLECULAR MEDICINE (2009)

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Challenges of characterizing proarrhythmic risk due to QTc prolongation induced by nonadjuvant anticancer agents

Nenad Sarapa et al.

EXPERT OPINION ON DRUG SAFETY (2008)

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Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial

Huw D. Thomas et al.

MOLECULAR CANCER THERAPEUTICS (2007)

Review Cell Biology

Poly(ADP-ribose):: novel functions for an old molecule

Valerie Schreiber et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2006)

Article Multidisciplinary Sciences

Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

H Farmer et al.

NATURE (2005)

Review Biochemistry & Molecular Biology

Cancer susceptibility and the functions of BRCA1 and BRCA2

AR Venkitaraman

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BRCA2 is required for homology-directed repair of chromosomal breaks

ME Moynahan et al.

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