HRD Harmonization Project
Homologous Recombination Deficiency Harmonization Project
The Homologous Recombination Deficiency (HRD) Harmonization Project supports the future use of assays that measure the HRD biomarker for treatment decision making. Friends is currently examining sources of variability across HRD tests and identifying opportunities for alignment while proposing solutions to improve agreement in the future.
Historically, cancer treatment involved and relied on chemotherapy, which attacks dividing cells throughout the body, including many cells that are not cancerous. In recent years, scientific innovation has allowed for the safe and effective use of targeted therapies, which can precisely attack cancer cells that have specific signals known as biomarkers, potentially providing more effective and safer treatments for patients. Since not all cancer cells have specific biomarkers targetable by current therapies, it is necessary to identify which patients have the biomarker and may benefit from specific targeted therapies. To help identify which patients have a specific biomarker, diagnostic developers have created tests, also known as assays.
Test developers have different approaches for how they identify a specific biomarker increasing variability across results from different tests. One such biomarker facing issues with harmonization is homologous recombination deficiency (HRD), which is used to determine which patients with certain types of cancer should be treated with a drug called a PARP inhibitor. A combination of factors is used to determine HR status, and different assays, or tests, use different approaches. This lack of harmonization can make it challenging for patients and providers to interpret the results of these tests.
To understand the variability in assays that test for HRD and determine solutions to harmonize the assays, Friends convened a group of test developers, patient advocates, providers, and government officials to address concerns about the lack of consistency in identifying HRD, its prognostic value for how well a treatment might work, and its use as a predictive biomarker for how a patient’s prognosis might differ due to the presence of the biomarker. During the first phase of the project, the group conducted a landscape analysis of how HRD is used and defined to establish a baseline understanding of inconsistencies across tests and to propose common terminology.
Phase 2 of the project works to align assays that measure HRD. The group identified samples that each test developer involved in the project could analyze using their HRD assay and then report the HR status, or whether the sample has HRD or not. The HR status will be compared across assays to understand the level of agreement among the assays. These results will be used to work towards defining where there are differences across assays and inform solutions to harmonize the results.
Friends’ HRD Harmonization Project will help determine the amount of agreement among assays that measure HRD and propose solutions to improve agreement in the future. If assay developers use agreed upon solutions in their assays, providers and patients will have more consistent results regardless of which assay is used to measure HRD. Without Friends coordination and support from collaborative sponsors, groups may never align on a solution to improve consistency across assays and interpreting results from assays would be more challenging for patients and providers.
- The Phase 1 Publication in the Oncologist describes opportunities and best practices to align the definition of HRD and the parameters that contribute to the determination of HR status.
Phase 1: AbbVie, ACT Genomics, Ambry Genetics, AstraZeneca, Arizona State University, Bristol Myers Squibb, Caris Life Sciences, EMD Serono, Inc., the U.S. Food and Drug Administration (FDA), Foundation Medicine, Inc., GlaxoSmithKline, Guardant Health, Inc., Janssen Pharmaceuticals, Merck & Co., Inc., Myriad Genetics, the National Cancer Institute (NCI), Novartis, Pfizer, Inc., Resolution Bioscience, Inc., Tempus Labs, Inc., Thermo Fisher Scientific, University of Alabama at Birmingham, University of Heidelberg
Phase 2: ACT Genomics, Amoy Diagnostics, AstraZeneca, Bayer, Bionano Genomics, Inc., Bristol Myers Squibb, DNAnexus, EMD Serono, Inc., European Organisation for Research and Treatment of Cancer (EORTC), FDA, Foundation Medicine, Inc., Guardant Health, Inc., Illumina, Inc., Invitae, MD Anderson Cancer Center, Merck & Co., Inc., Molecular Characterization Laboratory (MoCha) at Frederick National Laboratory, NCI, NeoGenomics, OmniSeq, Personalis, Inc., Pfizer Inc., Personal Genome Diagnostics (PGDx), SOPHiA GENETICS, Tempus Labs, Inc., Thermo Fisher Scientific, University of Alabama at Birmingham, University of Heidelberg