Biomarkers of Chinese advanced cancer patients based on real-world data: Actionable genomic alterations and tumor mutational burden

e14280 Background: Biomarkers would enrich patients(pts) with responsiveness to both targeted treatments and immunotherapy which have become a priority. However, molecular heterogeneous in actionable gene alterations and mutational loads need to be explored. In this study, based on a real world setting, Cancer Gene Panel (CGP） analysis was performed in a series samples of Chinese pts with advanced solid tumors, to delineate the landscape of actionable mutations and tumor mutational burden (TMB). Methods: 176 advanced pts were enrolled encompassing 19 common tumor types. All tissue samples were analyzed using next-generation sequencing with Acornmed panel including 808 genes. Results: The frequencies of genetic alterations among the most common driver genes were comparable to those reported by MSK-IMPACT (2018) ( TP53: 51.7% vs 44.8%; APC: 9.7% vs 9.8%; EGFR: 12.5% vs 7.7%; KRAS: 16.5% vs 13.6%; PIK3CA: 4.6% vs 12.0%; VHL: 4.0% vs 6.7%). 58.3% of pts with refractory solid tumors had at least one actionable mutation. Among those pts, 16.7% of them including CDK4, CDK6 or CDKN2A/B could benefit from palbociclib, and 32.1% of them including mTOR, PIK3CA, PTEN or STK11 could benefit from everolimus, and 61.9% of them including BRCA2, ARID1A, MSH1/2/6 or ATM could benefit from olaparib. Across all the specimens, the top 20% of TMB was 17.23 mutations/Mb, with a range of 0-48 mutations/Mb. The top 20% of TMB for each tumor type was 21.67(Bladder cancer), 17.23(Lung cancer), 16.45(Colorectal cancer), 11.04 (Renal cell cancer), 16.25 (Prostate cancer) , 19.70 (Hepatobiliary cancer), 14.78 (Esophagogastric cancer), 7.80 (Pancreatic cancer), 25.31 (undefined tumor) mutations/Mb respectively. Conclusions: This study indicates that most of pts with advanced refractory solid tumors have at least one actionable mutation, and matched therapies may confer clinical benefit. TMB fluctuated wildly across different cancer types, illustrating the unequal objective response rate of immunotherapy across various cancer type. Furthermore, CGP analysis in advanced pan-cancer pts can provide opportunities for targeted therapies and immunotherapy, especially in those with refractory cancer.