Abstract 3548: OKAIN: A comprehensive oncology knowledgebase for the interpretation of clinically actionable alterations

Abstract

Abstract Background: The increased use of Next-Generation Sequencing (NGS) in clinical genetic testing has resulted in the identification of several genetic variations with possible therapeutic implications. Several knowledgebases, such as OncoKB, have been curated to better understand the clinical implications of somatic mutations in cancer. While thorough annotation of gene variations of Chinese pharmaceuticals is not recorded in the majority of those databases. As a result, we developed OKAIN (https://szcube.origimed.com), an algorithm tool that assesses clinically actionable mutations using a precision oncology knowledge database. Methods: OKAIN employs a weighted evidence analysis system to deliver final clinical annotation outcomes for intricate variations. This process commences with a weighted analysis of all therapeutic efficacy evidence for a specific genomic variant related to a particular drug, to determine the highest degree of efficacy for that drug. The top efficacy level is then assessed against numerous variants of the gene, resulting in efficacy data for all variants of the gene in relation to the medication. Results: To date, OKAIN has collected 15,654 pieces of evidence on 471 genes associated with cancer. This comprises 2,600 pieces of Level A evidence (included in FDA/NMPA labeling or clinical professional guidelines) on 66 genes, 180 Level B evidence (included in extensive retrospective studies or prospective investigations) on 31 genes, 676 Level C evidence (included in small-scale retrospective studies or early-stage prospective studies) on 81 genes, and 5,562 Level D evidence (included in case reports and preclinical studies) on 188 genes. For Level A evidence, 864 pieces of evidence were derived from either the NMPA label or CSCO guidelines. As an illustration, Befotertinib was approved by NMPA as a first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) in adult patients with either EGFR exon 19 deletion or L858R mutation. This indicates that adult Chinese patients with locally advanced or metastatic NSCLC who have EGFR exon 19 deletion or L858R mutation can potentially experience benefits from administering Befotertinib. Conclusion: OKAIN acts as a precision oncology knowledgebase for the assessment of clinically actionable alterations, integrating exhaustive data related to cancer-associated genomic variants and therapeutic efficacy. It is a beneficial tool for medical professionals and patients, providing an enhanced means of understanding and approaching precision oncology. Citation Format: Zhenhua Yang, Mingmin Wang, Hongli Qin, Yanfei Yu, Yufeng Zheng, Ziang Li, Xinxiu Meng, Xiaowei Dong, Liwei Wang, Kai Wang, Aodi Wang. OKAIN: A comprehensive oncology knowledgebase for the interpretation of clinically actionable alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3548.