The Effect of Renal Impairment on the Pharmacokinetics and Safety of Talazoparib in Patients with Advanced Solid Tumors

被引:7
作者
Durairaj, Chandrasekar [1 ]
Chakrabarti, Jayeta [2 ]
Ferrario, Cristiano [3 ]
Hirte, Holger W. [4 ]
Babu, Sunil [5 ]
Piha-Paul, Sarina A. [6 ]
Plotka, Anna [7 ]
Hoffman, Justin [1 ]
Shi, Haihong [8 ]
Wang, Diane D. [1 ]
机构
[1] Pfizer Inc, Clin Pharmacol, 10555 Sci Ctr Dr, San Diego, CA 92121 USA
[2] Pfizer Ltd, Surrey, England
[3] McGill Univ, Jewish Gen Hosp, Montreal, PQ, Canada
[4] Juravinski Canc Ctr, Hamilton, ON, Canada
[5] Ft Wayne Med Oncol & Hematol, Ft Wayne, IN USA
[6] Univ Texas MD Anderson Canc Ctr, Invest Canc Therapeut, Houston, TX 77030 USA
[7] Pfizer Inc, Collegeville, PA USA
[8] Pfizer Inc, Groton, CT 06340 USA
关键词
D O I
10.1007/s40262-020-00983-y
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background Pharmacokinetic (PK) studies suggest that talazoparib is primarily eliminated unchanged via renal excretion. The current study investigated how varying degrees of renal impairment may affect the PK of talazoparib, and evaluated the safety and tolerability of talazoparib, in patients with advanced solid tumors with/without renal impairment. Methods Patients with advanced solid tumors and normal renal function or different degrees of renal impairment measured by estimated glomerular filtration rate (eGFR: mild = 60-89, moderate = 30-59, severe = 15-29 mL/min/1.73 m(2)) were enrolled in this open-label, non-randomized, phase I study. Talazoparib was administered orally at 0.5 mg/day for 22 days. Primary PK parameters included the area under the plasma concentration-time curve from 0 to 24 h (AUC(0-24)) and maximum observed plasma concentration (C-max) at steady state (Day 22). Safety and tolerability were also investigated. Results Thirty-four patients were enrolled. At Day 22, compared with patients with normal renal function (n = 9), patients with mild (n = 9), moderate (n = 8), or severe (n = 8) renal impairment had a 12.2%, 43.0%, and 163.3% increase in talazoparib AUC(0-24), and a 11.1%, 31.6%, and 89.3% increase in talazoparib C-max, respectively. Talazoparib was generally well tolerated, and overall there were no notable differences in the treatment-emergent adverse event profile across renal function groups. Conclusions Exposure to talazoparib increased with worsening renal impairment. Overall, this study confirms current dosing recommendations in patients with mild and moderate renal impairment (1 mg/day and 0.75 mg/day, respectively) and indicates that a lower starting dose of 0.5 mg/day should be considered for patients with severe renal impairment.
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收藏
页码:921 / 930
页数:10
相关论文
共 16 条
[1]   Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers [J].
de Bono, Johann ;
Ramanathan, Ramesh K. ;
Mina, Lida ;
Chugh, Rashmi ;
Glaspy, John ;
Rafii, Saeed ;
Kaye, Stan ;
Sachdev, Jasgit ;
Heymach, John ;
Smith, David C. ;
Henshaw, Joshua W. ;
Herriott, Ashleigh ;
Patterson, Miranda ;
Curtin, Nicola J. ;
Byers, Lauren Averett ;
Wainberg, Zev A. .
CANCER DISCOVERY, 2017, 7 (06) :620-629
[2]   Evaluation of the effect of P-glycoprotein inhibition and induction on talazoparib disposition in patients with advanced solid tumours [J].
Elmeliegy, Mohamed ;
Lang, Istvan ;
Smolyarchuk, Elena A. ;
Chung, Chin-Hee ;
Plotka, Anna ;
Shi, Haihong ;
Wang, Diane .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2020, 86 (04) :771-778
[3]   Quality of life with talazoparib versus physician's choice of chemotherapy in patients wits advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA ease III trial [J].
Ettl, J. ;
Quek, R. G. W. ;
Lee, K. -H. ;
Rugo, H. S. ;
Hurvitz, S. ;
Goncalves, A. ;
Fehrenbacher, L. ;
Yerushalmi, R. ;
Mina, L. A. ;
Martin, M. ;
Roche, H. ;
Im, Y. -H. ;
Markova, D. ;
Bhattacharyya, H. ;
Hannah, A. L. ;
Eiermann, W. ;
Blum, J. L. ;
Litton, J. K. .
ANNALS OF ONCOLOGY, 2018, 29 (09) :1939-1947
[4]  
European Medicines Agency, 2019, TALZENNA TALAZOPARIB
[5]  
European Medicines Agency, 2019, ASSESSMENT REPORT TA
[6]  
European Medicines Agency, 2015, GUIDELINE EVALUATION
[7]   Talazoparib has no clinically relevant effect on QTc interval in patients with advanced solid tumors [J].
Hoffman, Justin ;
Chakrabarti, Jayeta ;
Plotka, Anna ;
Naraine, Adriana Milillo ;
Kanamori, David ;
Moroose, Rebecca ;
Linh Nguyen ;
Wang, Diane ;
Wainberg, Zev A. .
ANTI-CANCER DRUGS, 2019, 30 (05) :523-532
[8]   Talazoparib in Patients with a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial [J].
Hurvitz, Sara A. ;
Gocalves, Anthony ;
Rugo, Hope S. ;
Lee, Yung-Hun ;
Fehrenbacher, Louis ;
Mina, Lida A. ;
Diab, Sami ;
Blum, Joanne L. ;
Chakrabarti, Jayeta ;
Elmeliegy, Mohamed ;
DeAnnuntis, Liza ;
Gauthier, Eric ;
Czibere, Akos ;
Tudor, Iulia Cristina ;
Quek, Ruben G. W. ;
Litton, Jennifer K. ;
Ettl, Johannes .
ONCOLOGIST, 2020, 25 (03) :E439-E450
[9]   Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation [J].
Litton, Jennifer K. ;
Rugo, Hope S. ;
Ettl, Johannes ;
Hurvitz, Sara A. ;
Goncalves, Anthony ;
Lee, Kyung-Hun ;
Fehrenbacher, Louis ;
Yerushalmi, Rinat ;
Mina, Lida A. ;
Martin, Miguel ;
Roche, Henri ;
Im, Young-Hyuck ;
Quek, Ruben G. W. ;
Markova, Denka ;
Tudor, Iulia C. ;
Hannah, Alison L. ;
Eiermann, Wolfgang ;
Blum, Joanne L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (08) :753-763
[10]   PARP inhibitors: Synthetic lethality in the clinic [J].
Lord, Christopher J. ;
Ashworth, Alan .
SCIENCE, 2017, 355 (6330) :1152-1158