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Review of Toxicities of PARP Inhibitors in Metastatic Castrate Resistant Prostate Cancer

  • Udit Nindra
    Correspondence
    Address for correspondence: Udit Nindra, Liverpool Hospital Cancer Therapy Centre, Cnr Elizbeth & Goulburn Street, Liverpool, New South Wales 2170, Australia.
    Affiliations
    Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia

    School of Medicine, University of New South Wales, Sydney, NSW, Australia
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  • Jun Hee Hong
    Affiliations
    Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia

    School of Medicine, University of New South Wales, Sydney, NSW, Australia
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  • Bavanthi Balakrishnar
    Affiliations
    Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia
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  • Abhijit Pal
    Affiliations
    Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia

    School of Medicine, University of New South Wales, Sydney, NSW, Australia
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  • Wei Chua
    Affiliations
    Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia

    School of Medicine, University of New South Wales, Sydney, NSW, Australia

    School of Medicine, Western Sydney University, Sydney, NSW, Australia

    Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
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      Abstract

      There is emerging evidence for the use of poly (ADP-ribose) polymerase inhibitors (PARPi) in patients with mCRPC with patients harboring germline or somatic mutations deriving clinical benefit. However, the toxicity profile of PARPi in mCRPC is not well established. In March 2022 a literature search was conducted across 4 databases – Medline, PubMed, Cochrane Library and Embase. In total, 14 relevant studies were identified cumulating in 2066 patients that were treated with PARPi. The overall ORR to PARPi alone or in combination with other therapy was 37% (246/666). In 5trials that investigated PARPi alone, the ORR was 39% (141/361). Treatment emergent adverse events (TEAEs) of any grade were reported in 96% (1034/1080) in PARPi treatment arms. TEAEs of grade >= 3 were reported in 57% (611/1080). 45% (457/1006) experienced treatment interruption whilst 31% (310/989) required dose reductions. 11% (114/1006) of patients had their treatment discontinued directly as the result of toxicity associated with the trial medications. The most common hematological toxicity was anemia, reported in 490/1160 (42%) patients. and lowered white blood cell count were the next 2most common toxicities, reported in 186/655 (28%) and 133/729 (18%) respectively. The 3most common non-hematological toxicities reported were nausea, fatigue and anorexia reported in 440/1013 (43%), 340/1013 (34%) and 274/1013 (27%) patients respectively. Overall, TRAEs associated with individual PARPi are still emerging with hematological toxicities being most apparent. Further toxicities will be informed from future clinical trials to allow improved treatment selection, education and management of toxicities in prostate cancer.

      Keywords

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