Abstract 3208: OncoKB, a precision oncology knowledgebase

Abstract OncoKB is a precision oncology knowledge base that annotates the oncogenic effects and clinical actionability of somatic alterations in cancer. Initially focused on solid tumors, OncoKB was introduced in 2016 with >200 genes and almost 3000 somatic alterations via a public website (oncokb.org) and through the cBioPortal for Cancer Genomics. OncoKB now contains annotations for >5000 alterations in 642 genes. This includes 30 Level 1 alterations (included in the FDA drug label; a growth of 114% since 2016), 15 Level 2 alterations (included in the NCCN guidelines; 50% growth), and 38 Level 3A alterations (predictive of drug response in well-powered clinical studies; 65% growth). OncoKB now also supports hematologic malignancies with two new levels of evidence systems that encompass diagnostic and prognostic implications (in addition to therapeutic implications) and 288 heme-specific alterations in 156 newly curated cancer-associated genes. At MSK, OncoKB is used for the annotation of 1000 molecular patient reports per month. To assess the clinical utility of OncoKB and changes in the frequency of actionable alterations, we performed a comparison between the AACR Project GENIE cohort from 2017 and the most recent one (Table 1). With an increased number of tumor types and greater inclusion of hematologic malignancies, the overall potential actionability rate increased by 3.6 percentage points. A shift in access to targeted cancer therapies is also observed, where Level 1 or 2 alterations increased over 5 percentage points and Level 3 alterations decreased by ~3 percentage points, perhaps reaping the benefits of recent successful phase III trials. August 2017 (v1.1)December 2019 (v7.2)AACR Project GENIE cohort size18,80480,248Tumor types with >100 samples3151Hematologic malignancies included29Level 1 or 2 annotation7.3%12.9%Level 3A annotation6.4%4.7%Level 3B annotation17.8%17.5%Total potential actionability31.5%35.1% While only a subset of patients with targetable alterations will benefit from treatments, there is ample evidence that targeted cancer therapies can have profound and durable clinical activity. Knowledgebases such as OncoKB have become a key component to support clinical decision making, and there is a continued need to expand their capabilities while maintaining a nuanced approach to annotation. Citation Format: Sarah Suehnholz, Hongxin Zhang, Moriah Nissan, Ritika Kundra, Jing Su, Lindsay LaFave, Kinisha Gala, Chad Vanderbilt, Maria Arcila, Marc Ladanyi, Michael Berger, Ahmet Zehir, Julia E. Rudolph, Paul Sabbatini, Ross Levine, Ahmet Dogan, Jianjiong Gao, David B. Solit, Nikolaus Schultz, Debyani Chakravarty. OncoKB, a precision oncology knowledgebase [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3208.