Medical Technology

First FDA Recognition for Tumor Marker Database

In the 20 years since the first targeted cancer therapy was approved more than 100 targeted cancer products are on the market or in development. These targeted drugs provide an alternative to chemotherapy’s carpet bombing- they are precise missiles that target specific genetic targets.

But which targets? Which tumors?

Oncologists are becoming more concerned about the confusion caused by the flood of biomarker information being thrown at them. Patients may also be missing out on potential treatments that could be effective.

All that has changed is the introduction of a new database.

The US Food and Drug Administration (FDA) last month, recognized the very first precision-oncology knowledge database linking genetic biomarkers to specific types of cancer. It was the Memorial Sloan Kettering Cancer Center’s Oncology Knowledge Base ( OncoKB).

“OncoKB’s roots are in the realization that it was asking too many clinical oncologists to memorize the rapidly growing number of specific tumor type-specific cancer mutations that could act as predictive biomarkers to targeted treatments,” said Debyani Chakravarty PhD Director of Research at OncoKB at the MSKCC’s Center for Molecular Oncology.

She added that “a clinical-decision-support program to provide this information in a point-of care setting was urgently required.”

OncoKB made its public debut on May 16, 2017, with the publication of a paper by Chakravarty and colleagues from JCO Precision Oncology. The database was able to provide evidence for more than 3000 cancer-related genes and 19 kinds of modifications. The database now includes 5685 genetic variants across 127 types of cancer.

In October, OncoKB became the first tumor-mutation database to be included in the FDA’s database recognition program.

Physicians and researchers can utilize an easy interface to evaluate evidence linking cancers, genetic biomarkers as well as drugs and other conditions.

“It’s difficult to determine what’s an actionable change and what’s not with this kind of information,” said Timothy Rebbeck PhD professor of cancer prevention at the Dana-Farber Cancer Institute, Boston, Massachusetts, who was asked for his opinion.

He added that the FDA nod for OncoKB makes sense: “[It’s] relevant for the FDA to be involved due to the treatment implications of these mutations.”

There are numerous cancer genomic databases. The list includes MSKCC’s own CBioPortal, as well as MyCancerGenome as well as the Precision Medicine Knowledge Base, Cancer Genome Interpreter, Cancer Driver Log, Tumor Portal and many more.

Chakravarty acknowledges that OncoKB is not the only one. She also said, “But that being stated OncoKB is now acknowledged by FDA as the first human somatic variant database.”

At the heart of OncoKB is a continuous curation process that involves more than 50 physicians and geneticists at the cancer center. “We have discovered a method to codify the scientific and medical expertise of MSK clinical oncologists”, said Chakravarty.

The team poses three seemingly simple questions: what the gene is and whether or not the mutation is oncogenic , and, if it is found in a specific cancer type, the therapeutic implications.

The data supporting them are assigned an OncoKB therapeutic degree of evidence on a scale that runs from “standard care” to “hypothetical.”

“What surprised me most was, even just gathering those three pieces information and making sure they were accurate was quite a challenge,” Chakravarty said.

FDA’s new recognition is considered partial as it doesn’t cover all aspects of OncoKB. The FDA hasn’t analyzed all the connections between biomarkers and drugs. OncoKB’s developers developed and submitted for recognition an FDA-specific zone listing oncology biomarkers that have been approved by the regulatory authorities.

OncoKB recognized by FDA offers similar information to the rest. However it is classified according to the FDA’s level-of-evidence system.

The FDA assigns one of three levels of evidence to genetic variants in regulatory submissions that it receives. FDA Level 1 is reserved to approved companion diagnostics for targeted therapies; FDA level 2 is assigned to “cancer variants that have evidence of clinical significance” and FDA level 3 to “cancer mutants with potential clinical significance”.

The FDA-recognized area of OncoKB currently contains 46 actionable genes in 40 cancer types with FDA Level-2 evidence, and 38 actionable genes in 33 cancer types with FDA Level-3 evidence.

The FDA first released guidelines on how to gain the recognition of genetic-variant databases in April. Medscape asked FDA why it took so long to approve the existence of a tumor-mutation database, given that cancer genomics is a vast, rapidly changing field.

Jim McKinney, FDA press officer, placed the responsibility on database developers to apply to be recognized as official. McKinney stated that “The FDA does not have the authority to direct other organizations to apply to the FDA for database recognition.” For OncoKB the review timeframe was “impacted by the COVID-19 virus which impacted agency resources.”

McKinney did not have access to the number of other oncology-related genetic databases the FDA is currently examining to recognize. McKinney did state that OncoKB has been partially recognized by the FDA. This means that “test developers can use these data to support medical validity of tumor-profiling test results in premarket submissions.”

Chakravarty said that commercial licensing requests, which typically have slid into the market at the rate of one request per week, “spiked” in the days after FDA recognition.

Chakravarty and Rebbeck have disclosed no relevant financial relations.

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Content Source: https://www.medscape.com/viewarticle/963334?src=rss

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