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The importance of using an FDA approved companion diagnostic


Duration: 5 min. read


Pathology & Laboratory Medicine

As a molecular pathologist, you’re always looking for ways to ensure that patients receive the best care available

Take Ki-67, for example. This is one of the oldest markers of cell proliferation, especially in assessing breast cancer pathology samples. Generally speaking, it’s a robust marker, one that has played different roles in the past. During my residency, physicians were routinely ordering the Ki-67 test for prognosis and the monitoring of therapeutic response and a Ki-67 test was frequently ordered as part of a panel that included hormone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2).

Traditionally, testing for Ki-67 has been performed by clinical laboratories as a laboratory developed test (LDT) pursuant to a federal law known as CLIA ’88. CLIA requires each properly certified CLIA laboratory to independently develop and validate its own LDTs. Therefore, labs may run their LDTs differently than other labs and the test specifications from one lab to another may vary. This does not mean that the LDTs are inaccurate, as CLIA requires validation and has other safeguards to help ensure test performance. However, in the realm of a companion diagnostic that is associated with a specific drug under FDA jurisdiction, it is important that physicians who prescribe the medication have a standardized test with national utility.

Historically, the clinical utility of Ki-67 was called into question. Some healthcare payers denied payment, with the justification something like, “Well, it hasn’t been proven that this test will significantly guide standard therapeutic decision-making and methods of measuring Ki-67 are not well standardized.” As a result, routinely performing a test for Ki-67, a gene whose presence indicates rapid reproduction of cancer cells, in breast cancer has been a subject of debate in the healthcare community.

Enter the game changer

The introduction of Eli Lilly’s VERZENIO™ (abemaciclib). VERZENIO is an oral solid dose medication for the treatment of certain cases of early and advanced or metastatic breast cancer; which was first approved by the FDA in September 2017.1 Specifically, VERZENIO is indicated in combination with endocrine therapy [for the treatment of] hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer in adults with disease progression following endocrine therapy, or as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

Shortly after VERZENIO’s launch for the early breast cancer indication, Quest Diagnostics Ki-67 MIB-1 pharmDx test was also approved by the FDA as the sole companion diagnostic for use in this setting. The Ki-67 MIB-1 pharmDx test is the only FDA-approved companion diagnostic for VERZENIO. The test assesses Ki-67 proliferation to evaluate whether a patient’s tumor may respond to VERZENIO in the early, node-positive breast cancer indication. Non-approved LDTs for Ki-67 are prohibited from being marketing or promoted for use as a companion diagnostic for VERZENIO.

Advantages of using Quest’s Ki-67 MIB-1 pharmDx test include:

1. Safety. The FDA approves companion diagnostics and regulates this field because the companion diagnostic becomes part of the FDA-approved drug labeling. By using an FDA approved companion diagnostic there is regulatory assurance that the test is standardized and has the appropriate validation for use with the specific drug.

2. Accuracy. The FDA approved the use of drugs such as VERZENIO that are CDK (cyclin-dependent kinase) inhibitors for individuals whose tumors have Ki-67 levels of 20 percent or higher. Because LDTs are developed individually in CLIA labs, there may be differences in the Ki-67 scores they report. FDA approval assures a standard methodology and result.

3. Decisiveness. Due to the historical variability in testing methodologies, the utility of Ki-67 as a predictive marker (as opposed to a prognostic marker) has been difficult to defend. With FDA approval as a companion diagnostic for VERZENIO, Quest’s pharmDx test can provide clear justification for prescribing the drug for individual patients for the approved indication.

4. Reproducibility. Knowledge that the Quest pharmDx Ki-67 companion diagnostic is FDA approved can elevate the awareness of the clinical pathologist, the oncologist, and the patient about the standardized reproducibility of the test; the FDA-approved package insert provides specific staining and scoring guidelines to ensure consistent results. Additionally, Ki-67 tests that do not have FDA approval as a companion diagnostic cannot be promoted for this use; only the Quest Ki-67 MIB-1 pharmDx test can be legally offered for this purpose.

5. Optimizing clinical utility and care. As one of the nation’s largest reference lab networks, Quest believes it’s crucial that the tests we perform have clinical utility to avoid unnecessary testing and help clinicians make accurate treatment decisions. We’re all operating in a cost-constrained healthcare environment with a finite number of medical dollars to spend on patient care, and of course we live by the pledge to first do no harm and prioritize patient safety. For all these reasons it’s important to choose the right test for the right purpose at the right time. In this indication, the choice of a companion diagnostic is clear.

Explore our growing list of oncology companion diagnostic tests, medical expertise, and technical solutions.

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Page Published: December 06, 2022

About the author

Harry Hwang, MD

Pathologist, Solid Tumor and Molecular Pathology

Phenopath Laboratories (a Quest Diagnostics Company)

Dr Hwang is a Molecular and Solid Tumor Pathologist and Director of Molecular Pathology at PhenoPath/Quest Laboratories in Seattle, WA.  He received his MD from the University of Pennsylvania and then his Pathology residency training (AP/CP) at the University of Washington.  Following his residency, he completed a diagnostic immunohistochemistry pathology fellowship and was also a postdoctoral research fellow working in the areas of cancer and the cell cycle.  Following his research work, Dr Hwang joined PhenoPath in 2008 and began overseeing the Molecular Pathology department as well as participating in the clinical and contract research immunohistochemistry services.

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