A pilot clinical trial of genomic-based therapy assignment with co-expression extrapolation (COXEN) in advanced/metastatic urothelial carcinoma.

Abstract

452 Background: We investigated the Co-eXpression ExtrapolatioN (COXEN) algorithm to select “next best therapy” for patients with advanced/metastatic urothelial cancer based on gene expression profiles. Methods: This is a single-arm, open label pilot study, that investigates the COXEN algorithm’s ability to use patients’ tumor gene expression models to predict sensitivities to 75 FDA-approved anticancer agents. The COXEN results were reviewed and discussed in a multi-disciplinary molecular tumor board. From that a treatment plan was chosen based on monotherapy clinical efficacy data in urothelial carcinoma, combination safety data (combinations of agents were allowed provided phase I data were available), side effect profile/tolerability, response or resistance to prior therapies, therapy contraindications, and feasibility of therapy. The objective of this study was to determine the feasibility of using COXEN as a clinical decision algorithm to make a real-time treatment decision within 21 days of specimen collection in patients with advanced/metastatic urothelial carcinoma. Results: A total of 8 patients enrolled and underwent tumor biopsy for COXEN analysis. Five out of 8 patients received COXEN therapy within 21 days of biopsy with various regimens including: vorinostat and etoposide; doxorubicin; sunitinib; doxorubicin and paclitaxel; erlotinib and nab-paclitaxel. There were no objective responses. The 5 patients treated with COXEN therapy had a median potential follow up of 36 months, median overall survival of 8.4 months (95% CI: 5.2 months – not estimable), and median progression free survival of 2.2 months (95% CI: 1.4 – 3.9 months). Grade 3 or 4 adverse events included: febrile neutropenia (n=2), hypophosphatemia (n=1) and hyponatremia (n=1). This trial was terminated early due to a lack of treatment responses. Conclusions: The COXEN algorithm is a unique personalized method for selecting therapy for patients with advanced urothelial carcinoma. Although the COXEN method was feasible, it did not demonstrate clinical efficacy in this small cohort of patients. Clinical trial information: NCT02788201.