About Ovarian Cancer

Without Maintenance, PFS Shortens With Each Recurrence²

mo, months; PFS, progression-free survival.

PFS was calculated from the day of first cycle of chemotherapy to the first disease progression; thereafter, it was calculated from the progression to subsequent progression or death.²

• With each recurrence, progression-free survival (PFS) and platinum-free intervals decrease and cumulative toxicity increases^2,4-6
• Median PFS after platinum-based chemotherapy for recurrent disease typically is <6 months without maintenance^6,7

Homologous Recombination Deficiencies Contribute to Platinum Responsiveness in Ovarian Cancers^8-10

Frequency of Homologous Recombination Deficiencies in Ovarian Cancer¹⁰

HRD testing is not widely used and cannot detect all DNA repair deficiencies; therefore, platinum responsiveness may be the best indicator of which patients will respond to a PARP inhibitor in a maintenance setting^8-10

• Platinum-based chemotherapies have served as the standard of care for ovarian cancer treatment for decades^8-10
• Platinum-based chemotherapies induce cross-linking between purine bases in DNA, lesions that require homologous recombination (HR) to repair^8-10
• In ovarian cancer patients who harbor a homologous recombination deficiency, compromised repair of DNA lesions is thought to contribute to their response to platinum-based chemotherapies^8,10
• The presence of mutations in BRCA genes is the most commonly observed type of HRD in ovarian cancer, however it is not the only one^10,11

When using platinum responsiveness to select patients, patients with and without BRCA mutation can derive benefit

BRCA, breast cancer susceptibility gene; PARP, poly(ADP-ribose) polymerase.

References: 1. Lorusso D, Mancini M, Di Rocco R, Fontanelli R, Raspagliesi F. The role of secondary surgery in recurrent ovarian cancer. Int J Surg Oncol. 2012;2012:613980. doi:10.1155/2012/613980. 2. Hanker LC, Loibl S, Burchardi N, et al; AGO and GINECO Study Group. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann Oncol. 2012;23(10):2605-2612. 3. National Cancer Institute. SEER Cancer Stat Facts: Ovarian Cancer. https://seer.cancer.gov/statfacts/html/ovary.html. Accessed December 10, 2017. 4. Fotopoulou C. Limitations to the use of carboplatin-based therapy in advanced ovarian cancer. EJC Suppl. 2014;12(2):13-16. 5. Dunton CJ. Management of treatment-related toxicity in advanced ovarian cancer. Oncologist. 2002;7(suppl 5):11-19. 6. Mirza MR, Monk BJ, Herrstedt J, et al; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164, and Supplementary Appendix. 7. 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):852-861. 8. da Cunha Colombo Bonadio RR, Fogace RN, Miranda VC, Diz MDPE. Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics (Sao Paulo). 2018;73(suppl 1):e450s. 9. Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 2015;5(11):1137-1154. 10. Morgan RD, Clamp AR, Evans DGR, Edmondson RJ, Jayson GC. PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer. Cancer Chemother Pharmacol. 2018;81(4):647-658. 11. Pennington KP, Walsh T, Harrell MI, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014;20(3):764-775.