FDA Grants Partial Recognition Status to Memorial Sloan Kettering Cancer Center Precision Oncology Knowledge Database

Solit, Chakravarty, Schultz

David B. Solit, MD, Debyani Chakravarty, PhD, and Nikolaus Schultz, PhD

OncoKB®, a comprehensive precision oncology knowledge database developed by researchers and physicians at Memorial Sloan Kettering Cancer Center, today received partial recognition status from the US Food and Drug Administration (FDA). It is the first database of somatic variants in cancer to be partially recognized by the FDA. (Somatic variants are alterations that develop later in life versus those that are inherited at birth, which are called germline variants.)

OncoKB includes information about the clinical and biological effects of more than 5,600 genomic changes in more than 680 cancer-associated genes. It builds on previously successful efforts at MSK to make the promise of personalized medicine a reality.

“Today, tumor genomic profiling is performed for almost every MSK patient with advanced cancer to ensure that we administer the cancer therapy most likely to be effective for that person,” explained David B. Solit, MD, director of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology at MSK. “Each tumor profiled is likely to have several mutations, and it can be challenging for clinicians to memorize which mutations are predictive of response to FDA-approved and experimental therapies or are important for understanding a patient’s prognosis or cancer subtype. OncoKB solves this dilemma by providing an expertly curated database of the biologic and clinical implications of thousands of cancer-associated mutations.”

“Part of the mission of precision oncology is empowering the clinical community to leverage the cancer genome of a patient’s tumor to guide treatment,” said Debyani Chakravarty, PhD, lead scientist of OncoKB and Assistant Attending in MSK’s Department of Pathology. “Currently, there are hundreds of targeted therapies that are either FDA-approved or being tested in clinical trials. What sets OncoKB apart is its active curation by disease experts and scientists at MSK who are at the forefront of cancer treatment and research. With the FDA partial recognition of OncoKB, the agency credentials our knowledge base as providing accurate, reliable, and clinically meaningful information to the medical and scientific communities.”

OncoKB is the result of a years-long collaboration across several departments at MSK. Spearheaded by Dr. Chakravarty and Nikolaus Schultz, PhD, head of Knowledge Systems in the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, the team is comprised of cancer biologists who carefully curated the literature, as well as software engineers, led by MSK computational oncologist JianJiong Gao, PhD, who developed the nimble software infrastructure. The database is currently maintained by the Marie Josée and Henry R. Kravis Center of Molecular Oncology.

The knowledge database collates specific information from various publicly available resources to capture the biologic and clinical information for individual mutations. These resources include disease-specific treatment guidelines from FDA drug labels, the National Comprehensive Cancer Network (NCCN), and other expert panels, as well as the scientific literature including proceedings of major scientific conferences such as the American Society of Clinical Oncology and the American Association for Cancer Research. Its ability to distinguish genomic “driver” variants (known to be responsible for tumor initiation or growth) from “passenger” variants (which do not contribute to tumorigenesis) is, in part, what makes it clinically valuable. Importantly, among the driver mutations, the platform’s output highlights those which are clinically actionable. The system performs this function because of a built-in feature called the Therapeutic Levels of Evidence scale that differentiates FDA-approved, and NCCN-guideline listed biomarkers for specific cancer drugs (Levels 1 and 2) from those that are investigational and associated with sensitivity to drugs currently being tested in clinical trials (Levels 3 and 4). Tumor type-specific information about known drug resistance mutations is also captured. The FDA partial recognition is specific to a section of OncoKB that is intended to support the development of next-generation sequencing (NGS) tests. A newly created tab on the database’s homepage maps variants with an OncoKB level of evidence to an FDA level of evidence and is a source of clinical validity for test developers.

Since data emerges so frequently, updates to the knowledge database are performed monthly, with priority given to new treatment-mutation associations that result from FDA drug approvals. All new information is reviewed by an expert committee of MSK clinicians, each of whom are leaders in their respective fields.

“We leverage the expertise of MSK physicians to ensure the information captured is accurate and current,” added Dr. Solit. “This is vital because the same mutation can have different biologic properties and therefore different clinical implications in different tumor subtypes. Each mutation must therefore be annotated for each tumor subtype.”

At MSK, OncoKB is used to automatically annotate the sequencing reports of over 12,000 patients per year whose tumors are analyzed by the FDA-cleared MSK-IMPACT test, which is carried out by MSK’s Molecular Diagnostics Service led by physician-scientist Marc Ladanyi. It is seamlessly integrated into MSK clinical patient charts so that physicians can use the information to make informed recommendations regarding treatment. The database is also used by MSK physicians and scientists in clinical research.

OncoKB is freely available for academic research use and its contents can also be licensed commercially. The next steps for OncoKB include the annotation of germline alterations, including several that have been validated as predictive of drug response, and the development of a clinical trial matching system.

“Precision medicine has changed the way we treat cancer, and OncoKB is a key resource as it helps ensure that each patient receives the treatments most likely to be effective for their specific cancer,” said Dr. Solit.