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
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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.
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