PI3KCA mutations in advanced urothelial carcinoma: A potential therapeutic target?

4582 Background: PI3KCA is frequently mutated in human cancer; however, information is scarce regarding its relevance in urothelial carcinoma (UC). We determined the prevalence of mutation and impact on clinical outcome of PI3KCA uniformly-treated patients with metastatic UC. Impact of PI3K and dual PI3K/mTOR inhibition was tested in vitro in UC cell lines with either H1047R or E545K mutation. Methods: 141 samples from invasive UC were scanned for mutations. Of those, complete clinical data was available from 85 cases treated with platinum-based combination chemotherapy for advanced or metastatic disease. DNA was extracted from FFPE material. Mutation status was determined by iPLEX sequencing and confirmed with hME sequencing. Overall survival (OS) was measured from beginning of treatment for metastatic disease to time of death or censored on the last known alive date. Cox proportional hazard model was used to assess the associations of PI3K mutational status and OS. Growth inhibitory effects of a specifi...