Tracking the FDA precision oncology drug approval landscape in OncoKB.
Authors: Suehnholz Sarah Phillips , Kundra Ritika , Zhang Hongxin , Nissan Moriah H , Lu Calvin , Dhaneshwar Amanda , Fernandez Nicole , Nandakumar Subhiksha , Arcila Maria E. , Ladanyi Marc , Berger Michael F. , Syed Aijazuddin , Brannon Angela Rose , Levine Ross L. , Dogan Ahmet , Drilon Alexander E. , Solit David B. , Schultz Nikolaus , Chakravarty Debyani 
Published: May 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 >7600 alterations in >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.