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PARP Inhibition, a New Therapeutic Avenue in Patients with Prostate Cancer

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Abstract

Up to 25% of patients with metastatic prostate cancer present with germline or somatic DNA damage repair alterations, some of which are associated with aggressive disease and poor outcomes. New data have brought poly(ADP-ribose) polymerase (PARP) inhibitors into sharp focus in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Olaparib improved survival after at least one new hormonal therapy (NHT) in a cohort of patients harboring BRCA1, BRCA2 or ATM mutations in the PROfound trial, while rucaparib, talazoparib and niraparib demonstrated compelling activity in phase II trials. While patients with prostate cancer and BRCA1 or BRCA2 mutations may derive greatest benefit of PARP inhibition, the magnitude of benefit seems much lower in the context of most other homologous recombination gene mutations. Several PARP inhibitors are currently developed in combination with conventional therapy, including chemotherapy, NHT, and alpha-particle emitters, at different disease stages. Herein, we review the rationale for PARP inhibition in patients with prostate cancer, discuss the impact of PARP inhibitors on outcomes, and explore underlying challenges for future developments.

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Fig. 1

Adapted from Sonnenblick et al. [27]

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Authors and Affiliations

  1. Department of Cancer Medicine, Paris Saclay University, Gustave Roussy, 114 rue Edouard Vaillant, 94 800, Villejuif, France

    Ronan Flippot, Anna Patrikidou, Mihaela Aldea, Emeline Colomba, Pernelle Lavaud, Laurence Albigès, Natacha Naoun, Alice Bernard-Tessier, Alina Fuerea, Mario Di Palma, Bernard Escudier, Yohann Loriot & Karim Fizazi

  2. Department of Radiation Oncology, Paris Saclay University, Gustave Roussy, Villejuif, France

    Pierre Blanchard & Mario Terlizzi

  3. Department of Nuclear Medicine, Paris Saclay University, Gustave Roussy, Villejuif, France

    Camilo Garcia

  4. Istituto Nazionale dei Tumori, Milan, Italy

    Giulia Baciarello

Authors
  1. Ronan Flippot
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  2. Anna Patrikidou
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  3. Mihaela Aldea
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  4. Emeline Colomba
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  6. Laurence Albigès
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  7. Natacha Naoun
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  8. Pierre Blanchard
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  9. Mario Terlizzi
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  10. Camilo Garcia
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  11. Alice Bernard-Tessier
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  13. Mario Di Palma
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  14. Bernard Escudier
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  15. Yohann Loriot
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  16. Giulia Baciarello
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  17. Karim Fizazi
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Corresponding author

Correspondence to Karim Fizazi.

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No external funding was used in the preparation of this manuscript.

Conflicts of Interest

Ronan Flippot has received honoraria from Janssen, Ipsen, Bristol-Myers Squibb, MSD, and Pfizer, and has received travel expenses from Merck. Anna Patrikidou has received consulting fees from Basilea. Mihaela Aldea has received travel expenses from Sandoz. Emeline Colomba is a member of the Advisory Boards of Bristol-Myers Squibb, Ipsen, Sanofi, Glaxo-Smith Kline, MSD, Pfizer, Clovis, Novartis, and Eisai. Pernelle Lavaud has received travel expenses from Astellas, Ipsen, Janssen, and Mundipharma. Laurence Albigès has received consulting fees from Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Corvus Pharmaceuticals, Exelixis, Ipsen, Janssen, Merck, MSD, Novartis, Peloton Therapeutics, Pfizer, and Roche; research funding from Bristol-Myers Squibb; and travel expenses from Bristol-Myers Squibb and MSD. Bernard Escudier has received honoraria from Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Oncorena, Pfizer, and Roche/Genentech; consulting or advisory role fees from AVEO, Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Pfizer, and Roche/Genentech; research funding from Bristol-Myers Squibb; and travel, accommodations and expenses from Bristol-Myers Squibb, Ipsen, MSD, Pfizer, and Roche/Genentech. Yohann Loriot has received honoraria from Pfizer and Sanofi; consulting or advisory role fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Janssen, MSD Oncology, Roche, Seattle Genetics; research funding from AstraZeneca, Boehringer Ingelheim, Clovis Oncology, CureVac, Exelixis, Incyte, Janssen Oncology, Medivation, MSD Oncology, Nektar, Oncogenex, Pfizer, and Sanofi; and travel, accommodations and expenses from Astellas Pharma, AstraZeneca, Janssen Oncology, MSD Oncology, Roche, and Seattle Genetics. Giulia Baciarello has received honoraria from Astellas Pharma, Janssen Oncology, Roche, and Sanofi; consulting or advisory role fees from Astellas Pharma, Europharma, Janssen Oncology, Modra Pharmaceuticals, Roche, Sanofi, Simon-Kucher and Partners; and travel, accommodations and expenses from Amgen, Astellas Pharma, AstraZeneca, Ipsen, Janssen Oncology, and Sanofi. Karim Fizazi has received advisory fees from Amgen, Astellas, Astrazeneca, Bayer, Clovis, Janssen, MSD, Novartis/AAA, Sanofi, CureVac, and Orion. Natacha Naoun, Pierre Blanchard, Mario Terlizzi, Camilo Garcia, Alice Bernard-Tessier, Alina Fuerea, and Mario Di Palma have no conflicts of interest to declare.

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Authors' contributions

Data collection: Mihaela Aldea, Anna Patrikidou, Giulia Baciarello, Ronan Flippot. Data analysis, redaction, proofing: all authors.

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Flippot, R., Patrikidou, A., Aldea, M. et al. PARP Inhibition, a New Therapeutic Avenue in Patients with Prostate Cancer. Drugs 82, 719–733 (2022). https://doi.org/10.1007/s40265-022-01703-5

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