Clinical News

UNITE Study - Identified potential molecular biomarkers of response to Enfortumab Vedotin in advance urothelial cancer


Abstract: A retrospective analysis of the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) database was presented at the 2023 ASCO Genitourinary Cancers Symposium. Through the next generation sequencing, the study analyzed several molecular biomarkers to identify the correlation between specific biomarkers and the efficacy of enfortumab vedotin.

Enfortumab vedotin is an antibody drug conjugate (ADC) that targets Nectin-4 and gets approval to treat patients with treatment-refractory advanced urothelial carcinoma(prior treated with immunotherapy & platinum-based chemotherapy). However, there are limited data on molecular biomarkers that predict the outcome of this therapy. Therefore, in this retrospective study, researchers analyzed data from the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) database. Several molecular biomarkers were assessed by next-generation sequencing (NGS), including tumor mutational burden (TMB), somatic alterations in at least 10% of patients, and the presence of one or more DNA damage response mutations. Of the 170 patients in the study, 69% had primary bladder tumors and 68% had received two or more lines of therapy prior to enfortumab vedotin. The result showed that the overall response rate was 47%, the median progression free survival was 6 months and the median overall survival was 12 months. First, in the specific alternations analysis, patients with ERBB2 and TSC-1 mutations were found to have higher overall response rates compared with wild-type. Second, median progression free survival was shorter in CDKN2A (HR = 1.7, 95% CI, 1.1-2.8), CDKN2B (HR = 2; 95% CI, 1.2-3.4), and MTAP (HR = 1.3; 95% CI, 0.7-2.6) alterations. Last, the patients with high tumor mutation burden (TMB-H) had longer overall survival (HR: 0.4; 95% CI, 0.2-0.9). In summary, tumor mutation burden and alterations in ERBB2, TSC1, CDKN2A, CDKN2B, and MTAP are associated with enfortumab vedotin treatment outcome in advance urothelial cancer and may require further researches to help inform clinical decision making.

Jindal T, Kilari D, Alhalabi O, et al. Biomarkers of response to enfortumab vedotin (EV) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of the UNITE study. Presented at: 2023 ASCO GU Cancers Symposium; February 16-18, 2023; San Francisco. Abstract #450.