Poly(ADP-ribose) Polymerase Inhibitor Olaparib in the Treatment of Ovarian Cancer: A Comprehensive Review of Current Literature

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Kamil Poboży
Julia Domańska
Paweł Domański


Purpose of the review: This comprehensive review aims to provide a summary of current research on the utilization of olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in the treatment of ovarian cancer. The review aims to highlight the key findings from recent clinical trials and assess the potential of olaparib as a targeted therapy for improving the prognosis of ovarian cancer patients.

Recent findings: Ovarian cancer remains a significant global health concern with high mortality rates. While optimal debulking surgery and platinum-based chemotherapy are the standard treatments, the recurrence rates remain substantial. The emergence of PARP inhibitors, particularly olaparib, has introduced a novel therapeutic approach that targets the genomic instability and DNA repair mechanisms in cancer cells. Notable clinical trials, such as SOLO1, SOLO2, and PAOLA-1, have demonstrated the effectiveness of olaparib in significantly improving progression-free survival, particularly in patients with BRCA mutations or homologous recombination deficiency. Additionally, combination therapies involving olaparib, such as those with bevacizumab or entinostat, have shown promising results.

Summary: The utilization of olaparib has brought about a paradigm shift in the treatment of ovarian cancer. Notably, it has shown significant improvements in progression-free survival and overall survival, particularly in patients with BRCA mutations or homologous recombination deficiency. The exploration of olaparib through various clinical trials and combination therapies continues to provide valuable insights and offer new prospects for ovarian cancer patients. Moreover, the growing understanding of PARP inhibitors holds the potential for further advancements in the prognosis of patients with this formidable condition.


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Poboży K, Domańska J, Domański P. Poly(ADP-ribose) Polymerase Inhibitor Olaparib in the Treatment of Ovarian Cancer: A Comprehensive Review of Current Literature. OncoReview [Internet]. 2023Jul.30 [cited 2023Dec.4];13(2(50):39-7. Available from: https://journalsmededu.pl/index.php/OncoReview/article/view/2784


1. Cancer Today. Estimated age-standardized incidence rates (World) in 2020, World, both sexes, all ages (excl. NMSC) (access: 19.05.2023).
2. Sambasivan S. Epithelial ovarian cancer: Review article. Cancer Treat Res Commun. 2022; 33: 100629. http://doi.org/10.1016/j.ctarc.2022.100629.
3. Stewart C, Ralyea C, Lockwood S. Ovarian Cancer: An Integrated Review. Semin Oncol Nurs. 2019; 35(2): 151-6. http://doi.org/10.1016/j.soncn.2019.02.001.
4. Jayson GC, Kohn EC, Kitchener HC et al. Ovarian cancer. Lancet. 2014; 384(9951): 1376-88. http://doi.org/10.1016/S0140-6736(13)62146-7.
5. Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2017; 41: 3-14. http://doi.org/10.1016/j.bpobgyn.2016.08.006.
6. Mittica G, Ghisoni E, Giannone G et al. PARP Inhibitors in Ovarian Cancer. Recent Pat Anticancer Drug Discov. 2018; 13(4): 392-410. http://doi.org/10.2174/1574892813666180305165256.
7. Song YJ. Prediction of optimal debulking surgery in ovarian cancer. Gland Surg. 2021; 10(3): 1173-81. http://doi.org/10.21037/gs-2019-ursoc-08.
8. Lheureux S, Braunstein M, Oza AM. Epithelial ovarian cancer: Evolution of management in the era of precision medicine. CA Cancer J Clin. 2019; 69(4): 280-304. http://doi.org/10.3322/caac.21559.
9. Redondo A, Guerra E, Manso L et al. SEOM clinical guideline in ovarian cancer (2020). Clin Transl Oncol. 2021; 23(5): 961-8. http://doi.org/10.1007/s12094-020-02545-x .
10. Kommoss S, Gilks CB, du Bois A et al. Ovarian carcinoma diagnosis: the clinical impact of 15 years of change. Br J Cancer. 2016; 115(8): 993-9. http://doi.org/10.1038/bjc.2016.273.
11. National Cancer Institute. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer—Patient Version (access: 19.05.2023).
12. Rooth C. Ovarian cancer: risk factors, treatment and management. Br J Nurs. 2013; 22(17): S23-S30. http://doi.org/10.12968/bjon.2013.22.Sup17.S23.
13. Tortolero-Luna G, Mitchell MF. The epidemiology of ovarian cancer. J Cell Biochem Suppl. 1995; 23: 200-7. http://doi.org/10.1002/jcb.240590927.
14. Goff B. Symptoms associated with ovarian cancer. Clin Obstet Gynecol. 2012; 55(1): 36-42. http://doi.org/10.1097/GRF.0b013e3182480523.
15. Gupta KK, Gupta VK, Naumann RW. Ovarian cancer: screening and future directions. Int J Gynecol Cancer. 2019; 29(1): 195-200. http://doi.org/10.1136/ijgc-2018-000016.
16. Elias KM, Guo J, Bast RC Jr. Early Detection of Ovarian Cancer. Hematol Oncol Clin North Am. 2018; 32(6): 903-914. http://doi.org/10.1016/j.hoc.2018.07.003.
17. Guan LY, Lu Y. New developments in molecular targeted therapy of ovarian cancer. Discov Med. 2018; 26(144): 219-29.
18. National Cancer Institute. NCI Dictionary of Cancer Terms. Genomic instability (access: 19.05.2023).
19. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability – an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010; 11(3): 220-8. http://doi.org/10.1038/nrm2858.
20. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646-74. http://doi.org/10.1016/j.cell.2011.02.013.
21. Yao Y, Dai W. Genomic Instability and Cancer. J Carcinog Mutagen. 2014; 5: 1000165. http://doi.org/10.4172/2157-2518.1000165.
22. Slade D. PARP and PARG inhibitors in cancer treatment. Genes Dev. 2020; 34(5-6): 360-94. http://doi.org/10.1101/gad.334516.119.
23. Manasaryan G, Suplatov D, Pushkarev S et al. Bioinformatic Analysis of the Nicotinamide Binding Site in Poly(ADP-Ribose) Polymerase Family Proteins. Cancers (Basel). 2021; 13(6): 1201. http://doi.org/10.3390/cancers13061201.
24. Ali AAE, Timinszky G, Arribas-Bosacoma R et al. The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks. Nat Struct Mol Biol. 2012; 19(7): 685-92. http://doi.org/10.1038/nsmb.2335 (correction in: Nat Struct Mol Biol. 2015; 22(8): 645).
25. Althaus FR, Richter C. ADP-ribosylation of proteins. Enzymology and biological significance. Mol Biol Biochem Biophys. 1987; 37: 1-237.
26. Morales J, Li L, Fattah FJ et al. Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit Rev Eukaryot Gene Expr. 2014; 24(1): 15-28. http://doi.org/10.1615/critreveukaryotgeneexpr.2013006875.
27. Ito S, Murphy CG, Doubrovina E et al. PARP Inhibitors in Clinical Use Induce Genomic Instability in Normal Human Cells. PLoS One. 2016; 11(7): e0159341. http://doi.org/10.1371/journal.pone.0159341.
28. Min A, Im SA. PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation. Cancers (Basel). 2020; 12(2): 394. http://doi.org/10.3390/cancers12020394.
29. Murai J, Huang SY, Das BB et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012; 72(21): 5588-99. http://doi.org/10.1158/0008-5472.CAN-12-2753.
30. Krastev DB, Wicks AJ, Lord CJ. PARP Inhibitors – Trapped in a Toxic Love Affair. Cancer Res. 2021; 81(22): 5605-7. http://doi.org/10.1158/0008-5472.CAN-21-3201.
31. Schreiber V, Illuzzi G, Héberlé E et al. De la découverte du poly(ADP-ribose) aux inhibiteurs PARP en thérapie du cancer [From poly(ADP-ribose) discovery to PARP inhibitors in cancer therapy]. Bull Cancer. 2015; 102(10): 863-73. http://doi.org/10.1016/j.bulcan.2015.07.012.
32. Ray-Coquard I, Pautier P, Pignata S et al. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019; 381(25): 2416-28. http://doi.org/10.1056/NEJMoa1911361.
33. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma . Nature. 2011; 474(7353): 609-15. http://doi.org/10.1038/nature10166 (correction in: Nature. 2012; 490(7419): 298).
34. Nijman SM. Synthetic lethality: general principles, utility and detection using genetic screens in human cells. FEBS Lett. 2011; 585(1): 1-6. http://doi.org/10.1016/j.febslet.2010.11.024.
35. Dréan A, Lord CJ, Ashworth A. PARP inhibitor combination therapy. Crit Rev Oncol Hematol. 2016; 108: 73-85. http://doi.org/10.1016/j.critrevonc.2016.10.010.
36. Robson M, Im SA, Senkus E et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation [published correction appears in N Engl J Med. 2017; 377(17): 1700]. N Engl J Med. 2017; 377(6): 523-33. http://doi.org/10.1056/NEJMoa1706450.
37. Tutt ANJ, Garber JE, Kaufman B et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021; 384(25): 2394-405. http://doi.org/10.1056/NEJMoa2105215.
38. Kaufman B, Shapira-Frommer R, Schmutzler RK et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015; 33(3): 244-50. http://doi.org/10.1200/JCO.2014.56.2728.
39. Mateo J, Carreira S, Sandhu S et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015; 373(18): 1697-708. http://doi.org/10.1056/NEJMoa1506859.
40. Golan T, Hammel P, Reni M et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019; 381(4): 317-27. http://doi.org/10.1056/NEJMoa1903387.
41. Charakterystyka produktu leczniczego. Lynparza (access: 19.05.2023).
42. Moore K, Colombo N, Scambia G et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018; 379(26): 2495-505. http://doi.org/10.1056/NEJMoa1810858.
43. DiSilvestro P, Banerjee S, Colombo N et al. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol. 2023; 41(3): 609-17. http://doi.org/10.1200/JCO.22.01549.
44. Banerjee S, Moore KN, Colombo N et al. Maintenance Olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021; 22(12): 1721-31. http://doi.org/10.1016/S1470-2045(21)00531-3 (correction in: Lancet Oncol. 2021; 22(12): e539)
45. 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. 2017; 18(9): 1274-84. http://doi.org/10.1016/S1470-2045(17)30469-2 (correction in: Lancet Oncol. 2017; 18(9): e510).
46. Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45(2): 228-47. http://doi.org/10.1016/j.ejca.2008.10.026.
47. Frenel JS, Kim JW, Aryal N et al. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on Olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial. Ann Oncol. 2022; 33(10): 1021-8. http://doi.org/10.1016/j.annonc.2022.06.011.
48. Poveda A, Floquet A, Ledermann JA et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo controlled, phase 3 trial. Lancet Oncol. 2021; 22(5): 620-31. http://doi.org/10.1016/S1470-2045(21)00073-5.
49. Penson RT, Valencia RV, Cibula D et al. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020; 38(11): 1164-74. http://doi.org/10.1200/JCO.19.02745.
50. Gao Q, Zhu J, Zhao W et al. Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA). Clin Cancer Res. 2022; 28(11): 2278-85. http://doi.org/10.1158/1078-0432.CCR-21-3023.
51. Ledermann JA, Pujade-Lauraine E. Olaparib as maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer. Ther Adv Med Oncol. 2019; 11: 1758835919849753. http://doi.org/10.1177/1758835919849753.
52. Ledermann J, Harter P, Gourley C et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012; 366(15): 1382-92. http://doi.org/10.1056/NEJMoa1105535.
53. Ledermann J, Harter P, Gourley C et al. Olaparib maintenance therapy in patients with platinum sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial . Lancet Oncol. 2014; 15(8): 852-61. http://doi.org/10.1016/S1470-2045(14)70228-1. (correction in: Lancet Oncol. 2015; 16(4): e158).
54. Poveda A, Lheureux S, Colombo N et al. Olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer patients without a germline BRCA1/BRCA2 mutation: OPINION primary analysis. Gynecol Oncol. 2022; 164(3): 498-504. http://doi.org/10.1016/j.ygyno.2021.12.025.
55. Ray-Coquard I, Leary A, Pignata S et al. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023; 34(8): 681-92. http://doi.org/10.1016/j.annonc.2023.05.005.
56. Lampert EJ, Zimmer A, Padget M et al. Combination of PARP Inhibitor Olaparib, and PD-L1 Inhibitor Durvalumab, in Recurrent Ovarian Cancer: a Proof-of-Concept Phase II Study. Clin Cancer Res. 2020; 26(16): 4268-79. http://doi.org/10.1158/1078-0432.CCR-20-0056.
57. Wethington SL, Shah PD, Martin L et al. Combination ATR (ceralasertib) and PARP (Olaparib) Inhibitor (CAPRI) trial in acquired PARP-inhibitor-resistant homologous recombination deficient ovarian cancer. Clin Cancer Res. 2023; CCR-22-2444. http://doi.org/10.1158/1078-0432.CCR-22-2444.
58. Konstantinopoulos PA, Gonzalez-Martin A, Cruz FM et al. EPIK-O/ENGOT-OV61: alpelisib plus Olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study). Future Oncol. 2022; 18(31): 3481-92. http://doi.org/10.2217/fon-2022-0666.
59. ClinicalTrials.gov. Alpelisib Plus Olaparib in Platinum-resistant/ Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected (access: 19.05.2023).
60. Gupta VG, Hirst J, Petersen S et al. Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of Olaparib in homologous recombination proficient ovarian cancer. Gynecol Oncol. 2021; 162(1): 163-72. http://doi.org/10.1016/j.ygyno.2021.04.015.
61. Cadoo K, Simpkins F, Mathews C et al. Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis. Gynecol Oncol. 2022; 166(3): 425-31. http://doi.org/10.1016/j.ygyno.2022.06.017.
62. Do KT, Kochupurakkal B, Kelland S et al. Phase 1 Combination Study of the CHK1 Inhibitor Prexasertib and the PARP Inhibitor Olaparib in High-grade Serous Ovarian Cancer and Other Solid Tumors. Clin Cancer Res. 2021; 27(17): 4710-6. http://doi.org/10.1158/1078-0432.CCR-21-1279.