Tracking the FDA precision oncology drug approval landscape in OncoKB.
Authors: Sarah Phillips Suehnholz, Ritika Kundra, Hongxin Zhang, Moriah H Nissan, Calvin Lu, Amanda Dhaneshwar, Nicole Fernandez, Subhiksha Nandakumar, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Aijazuddin Syed, Angela Rose Brannon, Ross L. Levine, Ahmet Dogan, Alexander E. Drilon, David B. Solit, Nikolaus Schultz, Debyani Chakravarty
Journal: Journal of Clinical Oncology (2024)

e13507 Background: OncoKB ( www.oncokb.org ), Memorial Sloan Kettering's (MSK) precision oncology knowledge base, is a comprehensive database that provides curated information about the oncogenic effect and clinical implications of genomic alterations in cancer. OncoKB assigns evidence-based levels of clinical actionability to individual mutational events in a tumor type-specific context and is the first somatic variant database to be partially recognized by the US-FDA. As of February 2024, OncoKB contains annotations for &gt;7600 alterations in &gt;840 cancer-associated genes, including 59 level-1 or 2 genes (standard care, specified in the FDA-drug label or professional guidelines), 8 level-3A and 12 level-4 genes (predictive of drug response based on well-powered clinical studies or compelling biological evidence respectively). As the field of precision oncology continues to evolve with the identification of new molecular targets and development of novel drug/drug combinations, we sought to provide OncoKB users with a resource that quantitates the landscape of FDA-approved precision oncology therapies in real-time. Methods: To provide clinicians with an easily accessible and transparent list of FDA-approved drugs that require molecular biomarker testing to determine patient eligibility for use of the drug, we curated and categorized all FDA-approved oncology drugs from the FDA’s Oncology / Hematologic Malignancies Approval Notifications webpage from 1998 to present. For each drug we recorded its mechanism of action and whether it qualifies as a targeted therapy (a cancer drug that binds to or inhibits a specific protein target) or a precision oncology therapy (a drug that is most effective in a molecularly defined subset of patients and for which pre-treatment molecular profiling is required for optimal patient selection). For all precision oncology therapies we further listed the FDA-recognized biomarker(s) from the FDA-drug label and determined whether a DNA-based method could be used for biomarker detection. The data are publicly available via an interactive and downloadable table on OncoKB’s Oncology Therapies page , which is updated on a bi-monthly basis. Results: Between June 1998 and January 2024, 217 novel oncology drugs were FDA-approved, 83.4% (n=181) of which were classified as targeted therapies. Greater than half (51.9%, n=94) of targeted therapies were classified as precision oncology therapies. Currently, 52 genes as well as MSI-H and TMB-H status are FDA-recognized biomarkers of treatment response. Over the past five years, 75 novel oncology drugs were FDA-approved, 46 (61.3%) of which were precision oncology therapies. Conclusions: OncoKB’s publicly available Oncology Therapies page provides insight into the pace of growth of the precision oncology drug landscape and serves as a complementary tool for clinicians who utilize OncoKB to determine whether a patient with cancer should receive biomarker testing.