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Review
Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer: lessons learned and future directions
  1. Giuseppe Caruso1,2,
  2. Federica Tomao1,
  3. Gabriella Parma3,
  4. Mariateresa Lapresa3,
  5. Francesco Multinu3,
  6. Innocenza Palaia1,
  7. Giovanni Aletti3,4 and
  8. Nicoletta Colombo3,5
  1. 1Department of Maternal and Child Health and Urological Sciences, University of Rome La Sapienza, Rome, Italy
  2. 2Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy
  3. 3Gynecologic Oncology Program, European Institute of Oncology IRCCS, Milan, Italy
  4. 4Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
  5. 5Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
  1. Correspondence to Dr Giuseppe Caruso, Department of Maternal and Child Health and Urological Sciences, University of Rome La Sapienza, Rome, Lazio, Italy; g.caruso{at}uniroma1.it

Abstract

Poly (ADP-ribose) polymerase inhibitors (PARPi) represent a new standard of care in the upfront treatment of advanced epithelial ovarian cancer to the point that the vast majority of patients now receive a PARPi, alone or in combination with the anti-angiogenic bevacizumab, as part of their first-line maintenance therapy. The clinical benefit of PARPi is well established; however, much has changed since their introduction and several relevant questions have been raised and remain unresolved in the post-PARPi era. The decision-making process regarding the most appropriate first-line maintenance therapy could be challenging in clinical practice, especially in the homologous recombination-proficient setting, and several other factors need to be considered apart from the mutational status. Concerns regarding post-PARPi progression treatment have emerged, highlighting an unmet need to define a valid algorithm strategy. PARPi may not only compromise the response to further platinum due to cross-resistance mechanisms but the impact on subsequent non-platinum chemotherapy and surgery also remains unclear. Definitive results on the role of PARPi rechallenge are awaited, especially in the case of oligoprogression managed with locoregional treatment. Moreover, the updated overall survival data from the recurrent setting warrant caution in using PARPi as single agents for unselected patients. Several PARPi combination regimens are emerging for overcoming PARPi resistance and may become our new therapeutic armamentarium. This review discusses a set of clinically relevant issues in the PARPi era and provides a glimpse of future challenges and opportunities in ovarian cancer treatment.

  • Ovarian Cancer
  • Homologous recombination
  • Medical Oncology

https://doi.org/10.1136/ijgc-2022-004149

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    Footnotes

    • Twitter @gcarusomd, @Fmultinu, @giovanni_aletti

    • Contributors GC: conceptualization, data curation, investigation, methodology, resources, software, validation, visualization, writing - original draft, writing - review and editing. FT, GP, ML, FM, IP, GA: data curation, methodology, validation, visualization, writing - review and editing. NC: project administration, validation, supervision; writing - review and editing. All authors have read and agreed to the published version of the 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 NC reports fees for advisory board membership for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, and Roche; fees as an invited speaker for AstraZeneca, Novartis, Clovis Oncology, GSK, and MSD/Merck; and institutional research grants from AstraZeneca and Roche. She has also reported non-remunerated activities as a member of the European Society for Medical Oncology (ESMO) Guidelines Steering Committee and chair of the Scientific Committee of ACTO (Alleanza Contro il Tumore Ovarico). All the other authors declare no conflicts of interest.

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

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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