Insights from C-CAT repository: A novel approach to identifying appropriate patient populations for anticancer drug development using the clinicogenomic nationwide database in Japan.

11159 Background: The integration of Comprehensive Genomic Profiling (CGP) with real-world data (RWD) provides crucial insights for anticancer drug development to achieve precision oncology, therefore, the current global trend to construct as the national projects, yet its clinical impact remains underexplored. The therapeutic efficacy of each line of anti-cancer drug in various cancer types and the relationship between genetic alterations and the effect of anticancer drugs is needed to guide the direction of future drug development promptly and precisely. Methods: A comprehensive analysis was conducted on data from Japan's Center for Cancer Genomics and Advanced Therapeutics (C-CAT) repository between June 2019 and December 2023. Five genomic profiling assays for CGP testing were reimbursed by nation-wide insurance in Japan. Utilizing the clinicogenomic repository of C-CAT, registered data of therapeutic efficacy of anticancer drug including cytotoxic agents, molecular-targeted agents, and immune checkpoint inhibitors were evaluated in association with genetic alterations. Data on anticancer drug of patients (pts) with recurrent or metastatic disease were included in the analysis. Results: The C-CAT registry data encompassed 60,256 pts across 32 tumor organ sites, classified ontology by the OncoTree over 4.5 years. Of these patients, 30,234 were male, and 30,017 were female, with 5 classified as unknown. In terms of age, 31,919 pts were < 65. The most registered origins were colorectal (n=10,110), pancreas (n=8,069), biliary tract (n=5,030), breast (n=3,744), esophagus/stomach (n=3,734), prostate (n=3,701), ovarian/fallopian tube (n=3,521), lung (n=3,427), and soft tissue (n=2,568). TP53mutations (58.3%, n=35,102) were most prevalent, followed by KRAS (25.8%, n=15,521), APC (19.9%, n=11,919), NOTCH3 (14.1%, n=8,502), and PIK3CA (13.0%, n=7,861). The frequency of BRCA1/2mutation was 4.1% (n=2,479). Overall response rate (ORR) for the first-, second-, third-, and fourth-lines treatment were 35.7%, 23.3%, 19.4%, and 19.2%, respectively. Pts treated with cisplatin or carboplatin in the first-line treatment, who had TP53 mutations, showed a better ORR than those without (44.0% vs. 38.9%, p < 0.001). Similarly, pts with BRCA1/2mutation showed a better ORR than those without (53.9% vs. 41.4%, p < 0.001) in the first-line treatment. Conclusions: This study was the first to report the relationship between genetic alterations and the therapeutic effect of anticancer drugs in each line. This approach based on big data analysis potentially accelerates drug development in the appropriate patient population by identifying significant associations between specific genetic mutations and improved outcomes with certain chemotherapy regimens in various cancers.