- The BRCAwt population includes both HRD-negative and HRD-positive patients
- BRCA wild-type tumors are categorized as those tumors that do not have a BRCA mutation or a somatic BRCA mutation
Adapted from Farmer H et al, 2005.
The clinical significance of in vitro studies is unknown. Mechanism of action statements are not meant to imply efficacy.
BRCA1- or BRCA2-deficient and wild-type embryonic stem cells were treated with KU0068684, a small-molecule PARP inhibitor, in an in vitro colony formation assay to measure clonogenic survival after 10-12 days of continuous exposure.
Beyond BRCA status
Understanding BRCA and other alterations in DNA repair pathways
- PARP inhibitors exploit the tumor cell's inability to repair DNA5
Nearly 2/3 of tumors harbor some kind of DNA-repair deficiencies; however, standardized tests do not conclusively identify all patients with these deficiencies6
BRCAwt patients have a narrow window of opportunity to benefit from a PARP inhibitor7-11
Current approved treatment settings for PARP inhibitors in ovarian cancer7-11
BRCA, breast cancer susceptibility gene; BRCAmut, BRCA mutated; BRCAwt, BRCA wild type; HRD, homologous recombination deficiency; PARP, poly(ADP-ribose) polymerase.
References: 1. 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. 2. 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. 3. 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. 4. Data on file. TESARO, Inc. 5. 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. 6. 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. 7. ZEJULA (niraparib) [package insert]. Waltham, MA: GSK, Inc; October 2019. 8. Avastin (bevacizumab) [package insert]. South San Francisco, CA: Genentech, Inc; May 2018. 9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer V.4.2017. © National Comprehensive Cancer Network, Inc. 2017 All rights reserved. Accessed January 16, 2018. To view the most recent and complete version of the guidelines, go online to NCCN.org. 10. Lynparza (olaparib) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2018. 11. Rubraca (rucaparib) [package insert]. Boulder, CO: Clovis Oncology, Inc; April 2018.