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An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions

An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and... Niraparib is an oral, potent, highly selective poly-ADP ribose polymerase 1 (PARP1) and PARP2 inhibitor. In most developed countries, it is approved as a maintenance treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with complete or partial response to platinum-based therapy. These approvals are based on results of randomised, double-blind, placebo-controlled trials, particularly the NOVA trial and more recently the PRIMA trial. In this comprehensive review, we delve into the scientific basis of PARP inhibition, discussing both preclinical and clinical data which have led to the current approval status of niraparib. We also discuss ongoing trials and biological rationale of combination treatments involving niraparib, with particular focus on antiangiogenic drugs, immune checkpoint inhibitors and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS/STING) pathway. In addition, we reflect on potential strategies and challenges of utilising current biomarkers for treatment selection of patients to ensure maximal benefit. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Oncology and Therapy Springer Journals

An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions

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Publisher
Springer Journals
Copyright
Copyright © The Author(s) 2021
ISSN
2366-1070
eISSN
2366-1089
DOI
10.1007/s40487-021-00167-z
Publisher site
See Article on Publisher Site

Abstract

Niraparib is an oral, potent, highly selective poly-ADP ribose polymerase 1 (PARP1) and PARP2 inhibitor. In most developed countries, it is approved as a maintenance treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with complete or partial response to platinum-based therapy. These approvals are based on results of randomised, double-blind, placebo-controlled trials, particularly the NOVA trial and more recently the PRIMA trial. In this comprehensive review, we delve into the scientific basis of PARP inhibition, discussing both preclinical and clinical data which have led to the current approval status of niraparib. We also discuss ongoing trials and biological rationale of combination treatments involving niraparib, with particular focus on antiangiogenic drugs, immune checkpoint inhibitors and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS/STING) pathway. In addition, we reflect on potential strategies and challenges of utilising current biomarkers for treatment selection of patients to ensure maximal benefit.

Journal

Oncology and Therapy – Springer Journals

Published: Dec 1, 2021

Keywords: Combined therapy; Niraparib; Ovarian Cancer; PARP inhibitors; Pharmacokinetics

References

  • Genome maintenance mechanisms for preventing cancer
    Hoeijmakers, JH
  • PARP inhibitors: Synthetic lethality in the clinic
    Lord, CJ; Ashworth, A
  • PARP-1, PARP-2 and ATM in the DNA damage response: functional synergy in mouse development
    Huber, A; Bai, P; de Murcia, JM; de Murcia, G
  • PARP1 Trapping by PARP Inhibitors Drives Cytotoxicity in Both Cancer Cells and Healthy Bone Marrow
    Hopkins, TA; Ainsworth, WB; Ellis, PA
  • Potential of the synthetic lethality principle
    Nijman, SM; Friend, SH
  • The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial
    Sandhu, SK; Schelman, WR; Wilding, G
  • Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors
    Jones, P; Altamura, S; Boueres, J
  • Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination
    Jones, P; Wilcoxen, K; Rowley, M; Toniatti, C
  • Abstract B168: The PARP inhibitor niraparib crosses the blood brain barrier in rodents and is efficacious in a BRCA2 mutant intracranial tumor model
    Mikule, KWK
  • Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
    Mirza, MR; Monk, BJ; Herrstedt, J
  • Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial
    Mirza, MR; Benigno, B; Dørum, A
  • Exploring and comparing adverse events between PARP inhibitors
    LaFargue, CJ; Dal Molin, GZ; Sood, AK; Coleman, RL
  • Safety and dose modification for patients receiving niraparib
    Berek, JS; Matulonis, UA; Peen, U
  • Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial
    Oza, AM; Matulonis, UA; Malander, S
  • Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
    Gonzalez-Martin, A; Pothuri, B; Vergote, I
  • Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial
    Moore, KN; Secord, AA; Geller, MA
  • Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer
    Telli, ML; Timms, KM; Reid, J
  • ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer
    Miller, RE; Leary, A; Scott, CL
  • Incorporation of bevacizumab in the primary treatment of ovarian cancer
    Burger, RA; Brady, MF; Bookman, MA
  • A phase 3 trial of bevacizumab in ovarian cancer
    Perren, TJ; Swart, AM; Pfisterer, J
  • The VEGF receptor neuropilin 2 promotes homologous recombination by stimulating YAP/TAZ-mediated Rad51 expression
    Elaimy, AL; Amante, JJ; Zhu, LJ
  • Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer
    Ray-Coquard, I; Pautier, P; Pignata, S
  • Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial
    Mirza, MR; Avall Lundqvist, E; Birrer, MJ
  • Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives
    Borella, F; Ghisoni, E; Giannone, G
  • cGAS-STING signaling in cancer immunity and immunotherapy
    Du, H; Xu, T; Cui, M
  • PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response
    Kim, C; Wang, XD; Yu, Y
  • Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy
    Zheng, J; Mo, J; Zhu, T
  • The Cytosolic DNA-Sensing cGAS-STING Pathway in Cancer
    Kwon, J; Bakhoum, SF
  • DNA-containing exosomes derived from cancer cells treated with topotecan activate a STING-dependent pathway and reinforce antitumor immunity
    Kitai, Y; Kawasaki, T; Sueyoshi, T
  • Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP
    Ablasser, A; Schmid-Burgk, JL; Hemmerling, I
  • PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression
    Jiao, S; Xia, W; Yamaguchi, H
  • Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models
    Wang, Z; Sun, K; Xiao, Y
  • PARP inhibition elicits STING-dependent antitumor immunity in Brca1-deficient ovarian cancer
    Ding, L; Kim, HJ; Wang, Q
  • PARP Inhibitor Efficacy Depends on CD8(+) T-cell Recruitment via Intratumoral STING Pathway Activation in BRCA-Deficient Models of Triple-Negative Breast Cancer
    Pantelidou, C; Sonzogni, O; De Oliveria, TM
  • Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma
    Konstantinopoulos, PA; Waggoner, S; Vidal, GA
  • A distinct pre-existing inflammatory tumour microenvironment is associated with chemotherapy resistance in high-grade serous epithelial ovarian cancer
    Koti, M; Siu, A; Clément, I
  • Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells
    Xu, H; Xian, J; Vire, E
  • Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer
    Strickland, KC; Howitt, BE; Shukla, SA