About Ovarian Cancer

Ovarian Cancer Recurrence Is Common, and Progression-free Survival Shortens With Each Recurrence1,2

  • With each recurrence, progression-free survival (PFS) and platinum-free intervals decrease and cumulative toxicity increases2,4-6
  • Median PFS after platinum-based chemotherapy for recurrent disease typically is <6 months6,7
PFS Shortens With Each Recurrence2
Graph showing median progression- free survival and recurrence

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

Homologous Recombination Deficiencies, Including BRCA Mutations, Contribute to Platinum Responsiveness in Ovarian Cancers8,9

  • Platinum-based chemotherapies have served as the standard of care for ovarian cancer treatment for decades8
  • Platinum-based chemotherapies induce cross-linking between purine bases in DNA, lesions which require homologous recombination (HR) to repair8
  • HR deficiencies (HRDs) occur when the function of HR genes is impaired by deleterious mutation or epigenetic repression8
  • In ovarian cancer patients who are HRD positive, compromised repair of DNA lesions is thought to contribute to their response to platinum-based chemotherapies8
  • Mutations in BRCA (breast cancer susceptibility gene) family genes are the most commonly observed type of HRD in ovarian cancer8,9

 

Frequency of Homologous Recombination Deficiencies in Ovarian Cancer9
Chart showing percent of women who are HRD negative, HRD positive and BRCA mutation

HRD, homologous recombination deficiency.

About 3 Out of 4 Women With Ovarian Cancer Do Not Have a BRCA Mutation and Have a Poorer Prognosis9,10

  • BRCA mutations include those occuring in the germline cells (gBRCA) and those arising sporadically within the tumor, also known as somatic BRCA (sBRCA) mutations11
  • Approximately 25% of patients with ovarian cancer harbor a BRCA mutation9
  • The remaining ≈75% of patients whose tumors are BRCA wild type are difficult to treat and have reduced chemosensitivity and poorer outcomes9,10
  • Historically, it was thought that patients whose tumors were BRCA wild type would not benefit from PARP inhibition12,13

 

BRCA Mutations Are Present in a Minority of Women With Ovarian Cancer9
BRCA mutations are present in a minority of women with ovarian cancer

BRCA, breast cancer susceptibility gene; gBRCAmut, germline BRCA mutation; PARP, poly(ADP-ribose) polymerase; sBRCAmut, somatic BRCA mutation.

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.  2. Hanker LC, Loibl S, Burchardi N, et al. 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. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164. 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. 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. 9. 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. 10. Hollis RL, Churchman M, Gourley C. Distinct implications of different BRCA mutations: efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer. Onco Targets Ther. 2017;10:2539-2551. 11. Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015;33(31):3660-3667. 12. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917-921. 13. Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913-917.