LynparzaTM (olaparib) is a first‐in‐class PARP inhibitor (PARPi) that allows women with BRCA mutated (BRCAm) platinum‐sensitive relapsed high-grade serous ovarian cancer to extend progression‐free survival (PFS).1-3
1. Weil, M.K. and Chen, M.D. 2011. PARP inhibitor treatment in ovarian and breast cancer. Curr Prob Cancer. 35(1),pp.7-50.
2. Ledermann, J. et al. 2012. Olaparib maintenance therapy in plat inum-sensitive re lapsed ovarian cancer. N Engl J Med. 366(15), pp.1382-1392.
3. Ledermann, J. et al. 2014. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomized phase 2 trial. Lancet Oncol. 15(8), pp.852-856.
4. Lynparza Summary of Product Characteristics
5. NICE Guidance, 2016. Olaparib for maintenance treatment of relapsed, platinum-sensitive, BRCA mutation-positive ovarian, fallopian tube and peritoneal cancer after response to second-line or subsequent platinumbased chemotherapy London: NICE. Available from:
Accessed [August 2017]
6. SMC Guidance 2016. Olaparib (Lynparza®) is accepted for use within NHS Scotland. Available from: [https://www.scottishmedicines.org.uk/files/advice/olaparib_Lynparza_Resub_FINAL_Oct_2016_revised_201016_for_website.pdf]
7. Cancer Research UK . Available from: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer#heading-Zero, Accessed: [August 2017]
8. Goff, B.A. et al. 2000. Ovarian carcinoma diagnosis. Cancer. 89(10), pp.2068-75.
9. Markman, M. et al. 2000. Second-Line Treatment of Ovarian Cancer. The Oncologist. 5(1), pp.26-35.
10. Hanker LC, Loibl S, Burchardi N, et al. The impact of second to line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann. Oncol. 2012;23(10):2605-2612.
11. Jelovac D, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J. Clin. 2011;61(3):183-203.
12. Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet. 2009;374(9698):1371-1382.
13. Ledermann, J. and Raja, F.A. et al. 2013. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 24(6), pp.24-32.
14. Trainer, A.H. et al. 2010. Moving towards personalized medicine. Int J Gynecol Cancer. 20(5), pp.704-716.
15. NICE Clinical guideline [cg164] 2015. Genetic counselling and genetic testing. Available [https://www.nice.org.uk/guidance/cg164/ifp/chapter/genetic-counselling-and-genetic-testing]. Accessed: [August 2017]
16. NHS Commissioning E01/P/b, 2015. Clinical Commissioning Policy: Genetic Testing for BRCA1 and BRCA2 Mutations. Available from: [https://www.england.nhs.uk/commissioning/wp-content/uploads/sites/12/2015/10/e01pb-brca-ovarian-cancer-oct15.pdf]. Accessed: [August 2017]
17. BGCS guideline, 2016. BGCS Guidelines for Epithelial Ovarian / Fallopian tube / Primary Peritoneal Cancer: Recommendations for Practice. Available from: [https://bgcs.org.uk/professionals/guidelines.html]. Accessed: [August 2017]
18. Pruthi S, et al. Mayo Clin Proc 2010; 85:1111–20.
19. Song, H. et al. 2014. The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. Hum Mol Genet. 23(17), pp.4703-4709.
20. Ledermann, J. et al. Appendix 7: Ovarian cancer: eUpdate published online. September 2016. Annals of Oncology 27 (Supplement 5): v145, 2016
21. Stavropoulo, A.V. et al. 2013. Prevalence of BRCA1 mutations in familial and sporadic Greek ovarian cancer cases. PLOS One. 8(3), 8:e58182, pp.1-10.
22. Aslop, K. et al. 2012. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: A report from the Australian Ovarian Cancer Study Group. J Clin Oncol. (30)21, pp. 2654–2663.
23. Robles-Diaz L, et al. Fam Cancer 2004;3:259–64.
24. Janavicius R. EPMA J 2010;1:397–412.
25. Balmaña J, et al. Ann Oncol 2011; 22(Suppl. 6):vi31–4.
26. Petrucelli N, et al. Genet Med 2010; 12:245–59.
27. Norquist, B.M. et al. 2012. Characteristics of women with ovarian carcinoma who have BRCA1 and BRCA2 mutations not identified by clinical testing. Gynecol Oncol. 2013. 128(3), pp.483-487.
28. Caldecott, K.W. 2003. Protein–proteins interactions during mammalian DNA single strand break repair. Biochem Soc Trans. 31 (Pt 1), pp.247-251.
29. Langelier, M.F. et al. 2014. PARP-2 and PARP-3 are selectively activated by 5 phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1. Nucleic Acids Res. 42(12), pp.7762-7775.
30. Hegde, M.L. et al. 2008. Early Steps in the DNA Base Excision/Single-Strand Interruption Repair Pathway in Mammalian Cells. Cell Res. 18(1), pp.27-4.
31. Aly, A. and Ganesan. S. 2011. BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability. Journal of Molecular Cell Biology. 3, pp. 66-74.
32. Weston, V.J. and Oldreive, CE. et al. 2010. The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. 2010. Blood. 116(22), pp. 4578-4587.
33. Rouleau, M. et al. 2010. PARP inhibition: PARP 1 and beyond. Nature Reviews, Cancer. 10(4), pp.293-301.
34. Girolimetti, G. et al. 2014. BRCA-Associated Ovarian Cancer From Molecular Genetics To Risk Management. Biomed Res. lnt, pp.1 -11.
35. Ledermann JA, Harter P, Gourley C, et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: An updated analysis from a Phase II, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2016.
36. Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D'Andrea AD. Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discov. 2015 Nov;5(11):1137-54.
37. Kurian, A.W. 2010. BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol. 22(1), pp.72-78.
38. Liu, G. et al. 2012. Differing clinical impact of BRCA1 and BRCA2 mutations in serous ovarian cancer. Pharmacogenomics. 13(13), pp.1523-1535.
NICE: The National Institute for Health and Care Excellence
SMC: Scottish Medicines Consortium
BGCS: British Gynaecological Cancer Society
ESMO: European Society for Medical Oncology
ECOG: Eastern Cooperative Oncology Group.
GB-5951 - August 2017