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PARP inhibitors: risk factors for toxicity and matching patients to the proper poly (ADP-ribose) polymerase inhibitor (PARPi) therapy
  1. Anca Chelariu-Raicu1,2,
  2. Fabian Trillsch1,
  3. Alexander Burges1,
  4. Bastian Czogalla1,
  5. Anna Hester1,
  6. Rahel Wuerstlein1,
  7. Nadia Harbeck1 and
  8. Sven Mahner1,2
  1. 1Department of Obstetrics and Gynecology, Breast Center, Gynecologic Cancer Center and CCC Munich, Ludwig Maximilians University Munich, Munich, Bayern, Germany
  2. 2German Cancer Consortium (DKTK), partner site Munich, German Cancer Research Center, Munich, Germany
  1. Correspondence to Dr Anca Chelariu-Raicu, Department of Obstetrics and Gynecology, Breast Center, Gynecologic Cancer Center and CCC Munich, Ludwig Maximilians University Munich, 81377 Munich, Bayern, Germany; Anca.Chelariu-Raicu{at}med.uni-muenchen.de

Abstract

The past 5 years have seen several fundamental advances in ovarian cancer, with important new insights towards novel therapeutic opportunities within the DNA repair pathway. With the incorporation of poly (ADP-ribose) polymerase inhibitors (PARPi) into maintenance treatment regimens, the management of short- and long-term adverse events are key clinical priorities. Currently, three different PARPi are clinically beneficial and have been approved for primary and recurrent ovarian cancer: olaparib, niraparib, and rucaparib. The duration of treatment with PARPi in patients with ovarian cancer varies; patients can receive treatment for up to 2 or 3 years in first-line setting, or continue treatment until unacceptable toxicity or progression occurs in recurrent disease. Despite their similar mechanisms of action, these three inhibitors have specific toxicity profiles, which may lead to dose interruptions or discontinuation of treatment. This review summarizes the current indications for PARPi, including their role in recurrent and first-line maintenance treatment for advanced ovarian cancer. We also outline dose modifications leading to treatment disruption and potential changes in quality of life after prolonged treatment. Finally, we highlight the patient groups most likely to benefit from each of the three different PARPi.

  • Homologous recombination
  • Ovarian Neoplasms
  • BRCA1 Protein
  • BRCA2 Protein

https://doi.org/10.1136/ijgc-2022-003990

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    Footnotes

    • Contributors Conception and design: All authors. Administrative support: N/A. Provision of study materials or patients: N/A. Collection and assembly of data: N/A. Data analysis and interpretation: N/A. Manuscript writing: All authors. Final approval of manuscript: All authors. The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests SM: research support, advisory board, honoraria and travel expenses from AbbVie, AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Medac, MSD, Novartis, Olympus, PharmaMar, Pfizer, Roche, Sensor Kinesis, Teva, Tesaro. FT: grants and personal fees from AstraZeneca, Clovis, Eisai, Medac, MSD, PharmaMar, Roche, and Tesaro/GSK outside the submitted work. NH: honoraria for lectures and/or consulting from Amgen, Astra Zeneca, Daiichi-Sankyo, Exact Sciences, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Sandoz, Seagen. AH: honoraria for lectures and/or consulting from Roche, Pfizer. No competing interests are reported by the other authors.

    • Provenance and peer review Not commissioned; externally peer reviewed.