2007P - Similar genetic profile in early and late-stage urothelial tract cancer suggests that early genomic testing bears the potential of timely personalized treatment in clinical trials

Background

Urothelial tract cancer (UTC) holds the thirteenth position in terms of mortality worldwide. There are still gaps in the knowledge of the mutational landscape in patients with advanced disease after multiple lines of prior treatment. This study compares the genomic, transcriptomics, and targeted treatment options between metastatic UTC (mUTC) patients treated with multiple lines of therapy to newly diagnosed, untreated Muscle Invasive Bladder Cancer (MIBC).

Methods

Genomic and clinical data was retrieved from two cohorts: Heavily treated mUTC patients referred to the Copenhagen Prospective Personalized Oncology (CoPPO) project at Rigshospitalet, University of Copenhagen. Biopsies in CoPPO were performed at the time of enrollment. Data for pre-treated MIBC UTC patients were acquired from the Cancer Genome Atlas Bladder Cancer (TCGA BLCA) cohort. Analyses included RNA count data and 523 highly important cancer-related genes (TrueSight Oncology-500) for comparative analysis.

Results

Patients from the CoPPO cohort (n = 31) had a lower median age at first-line treatment than the TCGA BLCA cohort (n = 412), with no significant gender disparity. The predominant histology was urothelial cell carcinoma in both cohorts. Genomic analysis revealed no significant difference between the top mutated genes in the two cohorts, specifically looking into DNA damage repair genes. Molecular subtyping indicated a higher frequency of neuroendocrine differentiation in the CoPPO cohort. Thirteen percent of patients in the CoPPO cohort received targeted therapy based on genomic findings, and 16% received non-targeted treatment, totaling 29% receiving CoPPO treatment (9 patients). The remaining 71% received best supportive care. Kaplan-Meier analysis showed a non-significant survival benefit for the intervention group in the CoPPO cohort.

Conclusions

When focusing on 523 highly relevant cancer genes, the mutational profile of mUTC patients who have undergone numerous treatment lines resembles that of newly diagnosed MIBC. These alterations can be targeted, indicating the potential advantage of early genomic testing for personalized treatment within clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Copenhagen University Hospital, Rigshospitalet.

Funding

Has not received any funding.

Disclosure

D.R. Stormoen: Financial Interests, Institutional, Research Grant: Pfizer, Merck Serono; Financial Interests, Personal, Advisory Board: MSD, Johnson & Johnson; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Serono. K.W. Mouw: Financial Interests, Personal, Advisory Role: EMD Serono, Pfizer, BMS, UroGen, Riva Therapeutics; Financial Interests, Institutional, Research Funding: Pfizer, Novo Ventures; Financial Interests, Personal, Writing Engagement: UpToDate; Financial Interests, Personal, Speaker, Consultant, Advisor: OncLive. Z. Szallasi: Financial Interests, Institutional, Research Funding: Lantern Pharma. M. Rossing: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca. F. Bagger: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Role: Immunitrack, Hervolution, Aida Oncology. H. Pappot: Financial Interests, Institutional, Research Grant: Pfizer, Merck Serono. All other authors have declared no conflicts of interest.