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Manage wisely: poly (ADP-ribose) polymerase inhibitor (PARPi) treatment and adverse events
  1. Ainhoa Madariaga1,
  2. Valerie Bowering1,
  3. Soha Ahrari2,
  4. Amit M Oza1 and
  5. Stephanie Lheureux1
  1. 1Medical Oncology & Hematology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
  2. 2Pharmacy, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
  1. Correspondence to Stephanie Lheureux, Medical Oncology & Hematology, Princess Margaret Hospital Cancer Centre, Toronto, ON M5G 2C, Canada; Stephanie.Lheureux{at}uhn.ca

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have transformed the treatment landscape in front-line and recurrent high-grade serous ovarian cancer. Maintenance strategies with PARPi have been assessed in randomized phase III trials in ovarian cancer; switch maintenance in the case of olaparib, niraparib, and rucaparib; and concurrent followed by continuation maintenance with veliparib. These studies have shown progression-free survival advantage with PARPi maintenance, with no major adverse changes in the quality of life; however, overall survival data remain immature to date. PARPi have also been incorporated in clinical practice as a single-agent treatment strategy in high-grade serous ovarian cancer, mainly in women who harbor alterations in the BRCA1/2 genes or have alterations in the homologous recombination deficiency (HRD) pathway. Contemporary studies are looking into potentially synergistic combination strategies with anti-angiogenics and immune checkpoint inhibitors, among others. The expansion of PARPi treatment has not been limited to ovarian cancer; talazoparib is licensed in patients with HER2-negative breast cancer with germline BRCA mutations (BRCAm), and front-line olaparib maintenance in patients with pancreatic cancer with germline BRCAm. Numerous studies assessing PARPi either in monotherapy or in combination with other agents are ongoing in multiple tumors, including prostate, endometrial, brain, and gastric cancers. Many patients are being treated with PARPi, some for prolonged periods of time. As a result, a thorough knowledge of the potential short- and long-term adverse events and their management is warranted to improve patient safety, treatment efficacy, and towards maintaining an appropriate dose intensity.

  • ovarian cancer
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This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Twitter @AinhoaMada

  • Correction notice Since the online publication of this article, the authors noticed that Table 3 was formatted incorrectly. Veliparib appeared under the table heading 'Platinum-sensitive' instead of the table heading 'Front-line'. This has now been corrected.

  • Contributors All authors contributed in writing and approving the final manuscript.

  • 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 VB was previously on the advisory board for olaparib with AZ and received a previous honorarium for a presentation with AZ. AO is on the steering committee of GSK, AZ and Clovis (uncompensated), and is PI on clinical trials for AZ, GSK, and Clovis. SL declares honaria from Roche, AZ, GSK, Merck, and is Co-Inv and PI on a number of different clinical trials.

  • Patient consent for publication Not required.

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

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