Precision medicine in advanced ovarian cancer: Incorporating homologous recombination deficiency (HRD) genomic instability testing to transform care -…

The treatment landscape for advanced ovarian cancer has evolved from where it was ten years ago, when at that stage it was very much a standard approach of surgery, chemotherapy, and then watch and wait to one where patients receive individualized care based on the unique features of their cancer, said Warner Huh, MD, FACOG, FACS, chair of the Department of Obstetrics and Gynecology at the University of Alabama at Birmingham School of Medicine. I dont think we have ever seen so many options to help improve clinical outcomes in the modern management of ovarian cancer than we have with the introduction of personalized medicine. To say its been transformative would be an understatement.

Identifying the Right Patients for Personalized MedicineThe introduction of PARP inhibitors for the treatment of certain women with advanced ovarian cancer is one recent example of how personalized medicine is transforming the way the disease is treated. Research has demonstrated that targeted treatment with PARP inhibitor-based regimens shows greater clinical benefit in women with homologous recombination deficient tumors as HRD is associated with an increased sensitivity to PARP inhibition. This group of patients accounts for approximately 50 percent of the advanced ovarian cancer population.

HRD is the functional impairment in a key DNA damage repair pathway that hinders a cell from fixing damaged DNA. Identifying HRD may suggest that a patient is a candidate for an appropriate PARP inhibitor-based regimen, which further blocks remaining DNA repair pathways causing the cancer cells to die. Given the relationship with HRD-positivity and PARP inhibitor regimens, HRD genomic instability testing is an important component of advanced ovarian cancer management.

Advanced ovarian cancer is a tough disease. When I see a patient is HRD-positive, I make sure she understands the results. I use it as an opportunity to share what it may mean for her care, said Dr. Huh. This conversation can also serve as a way to discuss the full treatment path ahead and set expectations for whats to come during different phases of her treatment journey.

Certain mutations that signal the presence of HRD, such as BRCA1/2 mutations, and other markers of genomic instability are identified through comprehensive biomarker testing.

In todays treatment landscape where cancer therapy is becoming increasingly personalized and biomarker-based, every woman diagnosed with advanced ovarian cancer should receive HRD genomic instability testing. Knowing that roughly half of our patients are HRD-positive, this testing can identify important information about her tumor which may better inform her treatment plan than testing for a BRCA mutation alone which is present in approximately just 25% of women with the disease, said Dr. Huh.

This puts into perspective the importance of HRD genomic instability testing. Without this test, we are not providing optimal information for informed decision-making about treatment, which is even more crucial given recent advances in medicine have brought us further than before as we aim to offer our patients hope.

However, given the various testing options across tumor types and the overall ongoing evolution in tumor-specific biomarker and genetic testing, gaps in knowledge about HRD genomic instability are complicating the testing landscape and hindering oncologists from consistently conducting the right tests immediately following diagnosis.

Elevating the Standard of Care by Addressing Gaps in KnowledgeAccording to a recent US survey 1 of 230 oncologists conducted by IntegraConnect and sponsored by AstraZeneca, many clinicians often underestimate the prevalence of HRD and the role it plays in treating cancer. The survey, which sought to better understand HRD genomic instability testing habits, barriers to testing and current knowledge gaps, showed that two-thirds of oncologists surveyed thought that fewer than 40 percent of women with advanced ovarian cancer are HRD-positive though the prevalence is much higher at 50 percent.2

The survey also revealed a common misunderstanding about the role of disease markers in ovarian cancer in this rapidly evolving space. Although three-quarters of respondents said that they were extremely or very familiar with HRD testing, 73% incorrectly said that homologous recombination repair (HRR) gene panels found in next-generation sequencing (NGS) tests help identify markers of genomic instability, when in fact, HRD genomic instability and BRCA are the only actionable biomarkers for use of PARP inhibition-based regimens known today.

HRR and HRD are both important features in DNA damage response, but the two terms are often confused. HRR is not a marker of genomic instability and is not a predictive biomarker for who may respond to PARP inhibition so an HRRm gene panel should not be used in place of an HRD test to help inform treatment decisions, said Dr. Huh.

Integrating HRD Genomic Instability Testing into the Full Treatment PlanNow, with a deeper understanding of the underlying biology of advanced ovarian cancer, oncologists have the tools to match the right treatment with the right patient.

Available tests for identifying HRD genomic instability in advanced ovarian cancer include: myChoice CDx from Myriad Genetics; FoundationOne CDx from Foundation Medicine; Caris Molecular Intelligence Comprehensive Genomic Profiling Plus (CGP+) from Caris Life Sciences; and Tempus xT from Tempus. However, 21% of oncologists surveyed did not select any of these HRD testing partners when presented with a list of 12 choices.3

These gaps demonstrate there is still more work to be done to ensure patients receive the right test as soon as possible following diagnosis to inform treatment decisions. One way to approach this is by adding a literal checklist to your clinical routine. In my practice, this checklist includes HRD genomic instability testing and germline testing at the earliest opportunity to ensure we are providing the optimal information to our patients. Simple things can make a big difference and the earlier you conduct HRD genomic instability testing, the better.

Were only at the tip of the iceberg in expanding the clinical utility of precision medicine. We can go even further to improve the treatment of advanced ovarian cancer particularly for the estimated one in two patients with HRD-positive tumors, said Dr. Huh. To sustain progress, the medical community needs to move beyond BRCA testing alone and conduct HRD genomic instability testing at the first opportunity. Without this information, physicians may not be able to optimize treatment decisions based on the patients individuals type of disease.

As we aim to work towards a cure for this devastating disease, we can enhance our care discussions by educating about comprehensive biomarker testing and ensuring that we order the right tests tests at the right time.

Learn more about incorporating HRD testing into clinical practice.

Dr. Warner Huh was compensated for his time associated with this article.

Original post:
Precision medicine in advanced ovarian cancer: Incorporating homologous recombination deficiency (HRD) genomic instability testing to transform care -...