Abstract 1189: OncoKB, MSK’s precision oncology knowledge base

Abstract

OncoKB, Memorial Sloan Kettering Cancer Center’s (MSK) precision oncology knowledge base (www.oncokb.org), is a comprehensive database that annotates the oncogenic effects and clinical actionability of somatic alterations in cancer. OncoKB supports variant interpretation by the cBioPortal for Cancer Genomics and is used to annotate >12,000 MSK patient sequencing reports annually. Since its introduction in 2016, OncoKB has expanded to include 5685 alterations in 682 genes, and in October 2021, it became the first somatic knowledge base to be partially recognized by the FDA. The scope of the OncoKB FDA recognition includes clinically actionable variants that map to an FDA level of evidence, the processes of variant curation, and policies regarding database oversight, personnel training and transparency of data sources and operations. This recognition credentials OncoKB as providing accurate, reliable and clinically meaningful information to the medical and scientific communities.

The OncoKB Therapeutic (Tx) Levels of Evidence categorize variants based on their tumor type-specific predictive value of sensitivity or resistance to matched standard care or investigational targeted therapies. To date, OncoKB includes 43 Level 1 genes (included in the FDA drug label), 23 Level 2 genes (included in professional guidelines), 25 Level 3A genes (predictive of drug response in well-powered clinical studies), 23 Level 4 genes (predictive of drug response based on compelling biological evidence), and 11 R1 or R2 resistance genes. Initially focused on solid tumors, OncoKB was expanded to include hematologic disease annotation in 2019 and introduced Diagnostic (Dx) and Prognostic (Px) levels of evidence. All three level of evidence systems (Tx, Dx and Px) are consistent with the guidelines for evidence-based categorization of somatic variants published as a joint consensus recommendation by AMP/ASCO/CAP.

OncoKB is governed by a Clinical Genomics Annotation Committee, composed of MSK physicians and scientists who ensure that the information captured is accurate and current, and an external advisory board composed of leaders in the clinical oncology and genomics communities who oversee OncoKB updates and progress. OncoKB curation rules and processes are transparent and documented in the OncoKB Curation Standard Operating Procedure, which is publicly available via the website. User feedback to OncoKB content is encouraged via the website and through cBioPortal. Queries or suggestions by OncoKB users are addressed by the OncoKB team within 72 hours.

OncoKB offers licenses for academic, commercial and hospital use, with which users can programmatically access the web API. Future work includes coverage of additional cancer-associated genes, annotation of germline alterations that are predictive of drug response and/or associated with increased heritable cancer risk and the development of a clinical trial matching system.

Citation Format: Sarah P. Suehnholz, Moriah Nissan, Hongxin Zhang, Ritika Kundra, Calvin Lu, Benjamin Xu, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Ahmet Zehir, Aijaz Syed, Julia E. Rudolph, Ross L. Levine, Ahmet Dogan, Jianjiong Gao, David B. Solit, Nikolaus Schultz, Debyani Chakravarty. OncoKB, MSK’s precision oncology knowledge base [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1189.