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Review
. 2022 Aug;7(4):100536.
doi: 10.1016/j.esmoop.2022.100536. Epub 2022 Jul 15.

Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon?

L Musacchio  1 , C M Cicala  2 , F Camarda  3 , V Ghizzoni  4 , E Giudice  4 , M V Carbone  4 , C Ricci  4 , M T Perri  4 , F Tronconi  5 , M Gentile  6 , V Salutari  4 , G Scambia  7 , D Lorusso  8
Affiliations
Review

Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon?

L Musacchio et al. ESMO Open. 2022 Aug.

Abstract

Immune checkpoint inhibitors (ICIs) have completely reshaped the treatment of many malignancies, with remarkable improvements in survival outcomes. In ovarian cancer (OC), however, this emerging class of drugs has not yet found a favorable use due to results from phase I and II studies, which have not suggested a substantial antitumoral activity of these agents when administered as monotherapy. Robust preclinical data seem to suggest that the combination ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) may result in a synergistic activity; furthermore, data from phase II clinical studies, evaluating this combination, have shown encouraging outcomes especially for those OC patients not suitable for platinum retreatment. While waiting for ongoing phase III clinical trial results, which will clarify the role of ICIs in combination with PARPis in the newly diagnosed OC, this review aims to summarize the preclinical data and clinical evidence available to date.

Keywords: PARP inhibitors; immune checkpoint inhibitors; immunotherapy; ovarian cancer.

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Conflict of interest statement

Disclosure DL reports research funding from Clovis, GSK, and MSD; personal interests with AstraZeneca, Clovis Oncology, GSK, PharmaMar, MSD; and financial interests with Clovis, Genmab, GSK, MSD. He also serves on the Board of Directors of GCIG (Gynecologic Cancer Inter Group). VS reports honoraria from GSK, PharmaMar, Roche, MSD, EISAI, Clovis, Oncology, and AstraZeneca. GS reports research support from MSD and honoraria from Clovis Oncology; serves as a consultant for Tesaro and Johnson & Johnson. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Wang Y., Ren F., Song Z., Wang X., Zhang C., Ouyang L. PARP inhibitors in patients with newly diagnosed advanced ovarian cancer: a meta-analysis of randomized clinical trials. Front Oncol. 2020;10:1204. - PMC - PubMed
    1. Ruscito I., Bellati F., Ray-Coquard I., et al. Incorporating PARP-inhibitors in primary and recurrent ovarian cancer: a meta-analysis of 12 phase II/III randomized controlled trials. Cancer Treat Rev. 2020;87 - PubMed
    1. American Cancer Society . American Cancer Society; Atlanta, GA: 2022. Cancer Facts & Figures 2022.
    1. Chang E., Pelosof L., Lemery S., et al. Systematic review of PD-1/PD-L1 inhibitors in oncology: from personalized medicine to public health. Oncologist. 2021;26(10):e1786–e1799. - PMC - PubMed
    1. Waldman A.D., Fritz J.M., Lenardo M.J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651–668. - PMC - PubMed

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