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Precision Medicine for Ovarian Cancer
Precision Medicine for Ovarian Cancer
Discover guideline-recommended actionable biomarkers in ovarian cancer.
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Biomarker Testing Is Transforming the Management of Ovarian Cancer
Biomarker testing in ovarian cancer can predict treatment response, prognosis, and suitability for targeted therapy, informing decisions at all stages of the treatment journey, from diagnosis through recurrence.1–3
Test All Newly Diagnosed Patients With Advanced Ovarian Cancer for Actionable Biomarkers
NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) for ovarian cancer recommend genetic risk evaluation, and germline and somatic testing (if not done previously), for all patients with advanced ovarian cancer.2
In the upfront setting, somatic testing may optimize the identification of molecular alterations that can inform the use of interventions for patients with homologous recombination deficiency (HRD).2 HRD can be caused by mutations in BRCA1 or BRCA2, or in the absence of a BRCA mutation, other measures of genomic instability, including loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST).3
NCCN Guidelines® recommendations2:
Comprehensive surgical staging and debulking (if needed)
Genetic risk evaluation and germline or somatic BRCA1/2m testing
Germline or somatic BRCA1/2m negative
Germline or somatic BRCA1/2m positive
HRD tissue testing
HRD negative
HRD positive
May inform magnitude of
benefit with PARPi maintenance therapy
Following on from the NCCN Guidelines, consider following the ASCO and SGO recommendations to carry out both germline and somatic testing, including HRD, at diagnosis for optimal treatment of patients with advanced ovarian cancer.3,4
ASCO and SGO provide actionable recommendations for biomarker testing. They recommend germline genetic testing for ovarian cancer susceptibility genes including BRCA1/2, and somatic testing for ovarian cancer BRCA1/2 in the absence of pathogenic germline variants.3,4 The SGO additionally states that somatic testing should determine HRD status (via measures of genomic instability including LOH, LST, TAI), to inform upfront treatment.3
Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian cancer V.3.2024. ©2024 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.
Recommendations from the SGO practice statement3
Approach 2:
Sequential Testing (Dependent Test Ordering)
Test for germline BRCA1/2 status. For patients with gBRCA1/2-negative status, also test for somatic BRCA1/2, LOH, HRD status
Approach 1:
Concurrent Testing (Independent Test Ordering)
Test for germline BRCA1/2 status and for somatic BRCA1/2, LOH, HRD status
Ovarian cancer diagnosis
Adapted from Gressel et al. 2024.3
ASCO, American Society of Clinical Oncology; BRCA1/2, BReast CAncer susceptibility gene 1/2; BRCA1/2m, BReast CAncer susceptibility gene 1/2 mutation; gBRCA, germline BReast CAncer susceptibility gene; HRD, homologous recombination deficiency; LOH, loss of heterozygosity; LST, large-scale state transitions; NCCN, National Comprehensive Cancer Network; PARPi, poly-ADP ribose polymerase inhibitor; SGO, Society of Gynecologic Oncology; TAI, telomeric allelic imbalance.
Test for All Actionable Germline and Somatic Biomarkers at Diagnosis and Upon Recurrence2,3
NCCN Guidelines recommend biomarker testing for patients with cancer, including but not limited to, ovarian cancer, fallopian tube cancer, or primary peritoneal cancer2
| What to test2 | When to test2 | |
|---|---|---|
| Biomarker | At diagnosis | Recurrence setting (if prior testing did not include these markers) |
| Germline BRCA1 and BRCA2 mutations | ||
| Somatic BRCA1 and BRCA2 mutations | ||
| LOH | ||
| HRD status | in the absence of gBRCA1/2 mutation | |
| FRα (FOLR1) | ||
| HER2 (by IHC) | ||
| MSI | ||
| MMR | ||
| TMB | ||
| BRAF | ||
| RET | ||
| NTRK | ||
BRAF, B-Raf proto-oncogene, serine/threonine kinase; BRCA1/2, BReast CAncer susceptibility gene 1/2; FDA, Food and Drug Administration; FOLR1, folate receptor alpha; g, germline; HER2, human epidermal growth factor receptor 2; HRD, homologous recombination deficiency; IHC, immunohistochemistry; LOH, loss of heterozygosity; MMR, mismatch repair; MSI, microsatellite instability; NCCN, National Comprehensive Cancer Network; NTRK, neurotrophic tyrosine receptor kinase; RET, rearranged during transfection; TMB, tumor mutational burden.
Approximately Half of Advanced Ovarian Cancer Cases Are HRD Positive5–8
HRD status (consisting of BRCA1/2 and genomic instability [GIS] measures) provides predictive, prognostic, and familial insights to inform upfront treatment decisions with PARPis.5–8
~50%
~50% HRD-negative/Unknowna
~25%
Non-BRCAm with evidence of LOH, TAI, LST
~17%
GermlineBRCAm
~8%
Somatic
BRCAm
~50%
HRD-positivea
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aHomologous recombination status can be characterized as HRD-positive (HRD) or HRD-negative (HRP).
Comprehensive HRD testing (including germline and somatic BRCAm and GIS testing) can provide9–13:
- Predictive insights by indicating treatment eligibility and providing information on the magnitude of benefit of PARPis in certain patients with ovarian cancer
- Prognostic insights—BRCA1/2m provides insight over the course of disease
- Familial insights—germline BRCA1/2m aids in familial risk assessment
BRCAm, BReast CAncer susceptibility gene mutation; GIS, genomic instability; HRD, homologous recombination deficiency; HRP, homologous recombination proficiency; LOH, loss of heterozygosity; LST, large-scale state transitions; PARPi, poly-ADP ribose polymerase inhibitor; TAI, telomeric allelic imbalance.
Sponsored Testing Program for Myriad MyChoice® CDx
Retest your patients with advanced ovarian cancer who were negative for
BRCA1/2 mutations at no added cost13,a
Help improve your identification of HRD-positive patients with a test that includes BRCA1/2 and genomic instability.
Enrollment
Visit the Myriad website by using the link below or call the sponsored testing program for Myriad MyChoice® CDx.
Helpline (877-283-6709)
Speak to a Precision Medicine team member about the sponsored testing program
This form is intended for US healthcare professionals only.
AstraZeneca requests this information in order to respond to your request and direct it to the appropriate Precision Medicine team member in your geography.
AstraZeneca does not use this for Sales or Marketing targeting. AstraZeneca does not share this information with third parties.
Required
*BRCA1/2, BReast CAncer susceptibility gene 1/2; CDx, companion diagnostic; HRD, homologous recombination deficiency.
Considerations for Your Practice
Investigate, action, or review MDT protocols for identifying patients eligible for biomarker testing, such as HRD status and BRCA1/2 mutations.
- Review and ensure all eligible patients with ovarian cancer receive a biomarker test as recommended by NCCN Guidelines and the 2024 SGO clinical practice statement2,3
- Include somatic as well as germline testing to increase the detection of mutations and inform treatment2,3
- Consider testing for HRD status or genomic instability in the absence of germline BRCA1/2 mutations2
- Find major testing labs in your area which can perform biomarker testing
- Find solutions to common challenges you may face during biomarker testing
BRCA1/2, BReast CAncer susceptibility gene 1/2; HRD, homologous recombination deficiency; MDT, multidisciplinary team; NCCN, National Comprehensive Cancer Network; SGO, Society of Gynecologic Oncology.
Helpful Resources
Check out these featured resources on biomarker testing in ovarian cancer.
Add your preferred resources to My Favorites—a personalized list of resources to download and share with your peers or patients.
FOR HCPS
Further than before: Latest perspectives in ovarian cancer care – highlightsWatch highlights of expert stakeholders discussing ovarian cancer, developments in care, principles of genomic testing, and optimizing the patient journey.
FOR HCPS
Further than before: The biomarker driven nature of ovarian cancerWatch Dr. Warner Huh share his perspective on the role of personalized medicine in ovarian cancer and how it has transformed the treatment landscape.
FOR HCPS
Leading the way: Approaches in biomarker testing for cancer treatment with Michelle ShillerWatch Dr. Michelle Shiller share her experience leading in biomarker testing standardization in advanced ovarian cancer. She discusses her motives to improve testing rates, challenges, approaches, and the outcome of these efforts.
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Connect with usReferences
- National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER). Cancer Statistics Review (CSR). 1975–2020 – Ovary. 2020; Accessed October 04, 2024. https://seer.cancer.gov/statistics-network/explorer/application.html?site=61&data_type=4&graph_type=2&compareBy=age_range&chk_age_range_9=9&chk_age_range_141=141&chk_age_range_157=157&relative_survival_interval=5&hdn_sex=3&race=1&stage=101&advopt_precision=1&advopt_show_ci=on&hdn_view=0&advopt_show_apc=on&advopt_display=1
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer. V.3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed October 04, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org
- Gressel GM, et al. Gynecol Oncol. 2024;181:170–178.
- Konstantinopoulos PA, et al. J Clin Oncol. 2019;38(11):1222–1245.
- Hoppe MM, et al. J Natl Cancer Inst. 2018;110(7):704–713.
- Frey MK, Pothuri B. Gynecol Oncol Res Pract. 2017;4:4.
- Cancer Genome Atlas Research Network. Nature. 2011;474(7353):609–615.
- Konstantinopoulos PA, et al. Cancer Discov. 2015;5(11):1137–1154.
- Mirza MR, et al. Ann Oncol. 2020;31(9):1148–1159.
- Pellegrino B, et al. ESMO Open. 2019;4:e000480.
- Heeke AL, et al. JCO Precis Oncol. 2018;2018:PO.17.00286.
- Bolton KL, et al. JAMA. 2012;307(4):382–390.
- Myriad Genetics. MyChoice® CDx HRD Companion Diagnostic Test. Accessed October 08, 2024. https://myriad.com/mychoicecdx-astrazeneca/
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.