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Systematic Review

PARP inhibitors: a tsunami of indications in different malignancies

    Gaëlle Haddad

    Hematology & Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

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    ,
    Marie Christelle Saadé

    Hematology & Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

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    ,
    Roland Eid

    Hematology & Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

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    ,
    Fady Gh Haddad

    Hematology & Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

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    &
    Hampig Raphael Kourie

    *Author for correspondence: Tel./Fax: +00 961 142 1630;

    E-mail Address: hampig.kourie@hotmail.com

    Hematology & Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

    Unité de Génétique Médicale, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

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    Published Online:22 Jan 2020https://doi.org/10.2217/pgs-2019-0113

    Abstract

    The evolution of precision medicine in the field of oncology has led to a radical change in the course of malignancies. PARP inhibitors are drugs that block the activity of the PARP enzyme responsible for base excision repair and have shown significant positive response when used for tumors lacking homologous recombination, namely high efficacy among BRCA-mutated tumors. Since 2014, when olaparib received an accelerated US FDA approval in ovarian cancer, we witnessed many other FDA approvals for olaparib, rucaparib, niraparib and talazoparib. Additionally, many Phase I, II and III trials were published presenting revolutionizing results. Other ongoing trials combined PARP inhibitors with checkpoint inhibitors. We aimed in this review to state the FDA approvals for PARP inhibitors in breast, ovarian, fallopian tube and primary peritoneal cancers, report the major published trials in high impact medical journals, and mention the ongoing trials combining these drugs with checkpoint inhibitors.

    References

    • 1. Shin SH, Bode AM, Dong Z. Precision medicine: the foundation of future cancer therapeutics. NPJ Precis. Oncol. 1, 12 (2017).
      MedlineGoogle Scholar
    • 2. A Baudino T. Targeted cancer therapy: the next generation of cancer treatment. Curr. Drug Discov. Technol. 12, 3–20 (2015).
      MedlineGoogle Scholar
    • 3. Dziadkowiec KN, Gąsiorowska E, Nowak-Markwitz E, Jankowska A. PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting. Menopausal Rev. 4, 215–219 (2016).
      Google Scholar
    • 4. Pommier Y, Huang SH, Das BB et al. 284 differential trapping of PARP1 and PARP2 by clinical PARP inhibitors. Eur. J. Cancer 48, 87 (2012).
      Google Scholar
    • 5. Tutt A, Robson M, Garber JE et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet Lond. Engl. 376, 235–244 (2010).
      Medline CASGoogle Scholar
    • 6. Audeh MW, Carmichael J, Penson RT et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 376, 245–251 (2010).
      Medline CASGoogle Scholar
    • 7. Gelmon KA, Tischkowitz M, Mackay H et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a Phase II, multicentre, open-label, non-randomised study. Lancet Oncol. 12, 852–861 (2011).
      Medline CASGoogle Scholar
    • 8. Ledermann J, Harter P, Gourley C et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N. Engl. J. Med. 366, 1382–1392 (2012).
      Medline CASGoogle Scholar
    • 9. Liu JF, Barry WT, Birrer M et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised Phase II study. Lancet Oncol. 15, 1207–1214 (2014).
      Medline CASGoogle Scholar
    • 10. Oza AM, Cibula D, Benzaquen AO et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised Phase II trial. Lancet Oncol. 16, 87–97 (2015).
      Medline CASGoogle Scholar
    • 11. Robson M, Im S-A, Senkus E et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 377, 523–533 (2017).
      Medline CASGoogle Scholar
    • 12. Pujade-Lauraine E, Ledermann JA, Selle F et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, Phase 3 trial. Lancet Oncol. 18, 1274–1284 (2017).
      Medline CASGoogle Scholar
    • 13. Moore K, Colombo N, Scambia G et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med. 379, 2495–2505 (2018).
      Medline CASGoogle Scholar
    • 14. Konstantinopoulos PA, Barry WT, Birrer M et al. Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion Phase Ib trial. Lancet Oncol. 20, 570–580 (2019).
      Medline CASGoogle Scholar
    • 15. Swisher EM, Lin KK, Oza AM et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, Phase II trial. Lancet Oncol. 18, 75–87 (2017).
      Medline CASGoogle Scholar
    • 16. Coleman RL, Oza AM, Lorusso D et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, Phase III trial. Lancet 390, 1949–1961 (2017).
      Medline CASGoogle Scholar
    • 17. Sandhu SK, Schelman WR, Wilding G et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a Phase 1 dose-escalation trial. Lancet Oncol. 14, 882–892 (2013).
      Medline CASGoogle Scholar
    • 18. Mirza MR, Monk BJ, Herrstedt J et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N. Engl. J. Med. 375, 2154–2164 (2016).
      Medline CASGoogle Scholar
    • 19. Moore KN, Secord AA, Geller MA et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, Phase II trial. Lancet Oncol. 20, 636–648 (2019).
      Medline CASGoogle Scholar
    • 20. González-Martín A, Pothuri B, Vergote I et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med. 381, 2391–2402 (2019).
      Medline CASGoogle Scholar
    • 21. Mirza MR, Åvall Lundqvist E, Birrer MJ et al. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol. 20, 1409–1419 (2019).
      Medline CASGoogle Scholar
    • 22. Litton JK, Rugo HS, Ettl J et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N. Engl. J. Med. 379, 753–763 (2018).
      Medline CASGoogle Scholar
    • 23. Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer 12, 237–251 (2012).
      Medline CASGoogle Scholar