ASCO GU 2021: Efficacy of Enfortumab Vedotin in Advanced Urothelial Cancer: Retrospective Analysis of the Urothelial Cancer Network To Investigate Therapeutic Experiences (UNITE) Study

( Advanced urothelial carcinoma has among the worst prognosis for tumors treated by genitourinary oncologists. Standard of care dictates that patients receive platinum-based induction chemotherapy. However, even with this treatment, rates of recurrence and disease progression are high and overall survival is quite short due to the development of chemotherapy resistance. Subsequent treatments may include immune checkpoint inhibition or targeted therapy. Recently, one of these targeted therapies which have gained FDA approval for patients with treatment-refractory advanced urothelial cancer is enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4. While enfortumab vedotin has been FDA approved, in a poster presentation at the 2021 ASCO GU Cancers Symposium, Dr. Koshkin and colleagues assessed its activity in particular patient subsets of interest including those with distinct histological variants.

Using the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) cohort, the authors performed a retrospective study of patients with advanced urothelial carcinoma treated with ≥1 dose of enfortumab vedotin as the standard of care (SOC) or on a clinical trial (if trial results already reported) at 12 US sites. The authors assessed objective response rate (ORR), as assessed by investigators for patients with at least one post-baseline scan or clear evidence of clinical progression, and compared ORR across subsets of interest.

The authors examined 184 patients with advanced urothelial carcinoma, who had a median age at diagnosis of 70 years, 80% of whom were men and 60% of whom had undergone definitive surgery. The preponderance had the primary disease in the bladder (70%) while 28% had upper tract disease. Based on the local review, most (72%) had pure urothelial histology, while 26% had at least a component of variant histology, most commonly squamous (14%), micropapillary (8%), or plasmacytoid (3%). 15% of patients had an ECOG performance status of 2 or greater, 37% had baseline neuropathy, 15% had diabetes, and 9% had renal dysfunction with a GFR≤30.

Enfortumab vedotin was given as monotherapy in 84% and as SOC in 58%. The vast majority (81%) had received one or more prior treatment in the metastatic setting.

The median time from diagnosis of metastatic disease to start of enfortumab vedotin was 11.7 (IQR: 4.3 – 20.5) months. Once initiated, the median duration of enfortumab vedotin treatment was 5.5 (IQR: 1.4 – 6.7) months. Among 84% of patients who were evaluable for response, the ORR 53% (8% complete response, 45% partial response) while 25% had stable disease and 21% had progressive disease. Median PFS and OS were not yet reached.

At the time of data cut-off (September 2020), most patients (55%) had stopped enfortumab vedotin (36% due to PD, 19% intolerance) and 65% were alive.

Among subgroups of interest, no statistically significant differences were noted between subgroup strata.


In conclusion, in this observational dataset, the authors demonstrate that responses to enfortumab vedotin were present across a variety of subgroups of patients with advanced urothelial cancer, with significant differences between subgroup strata.

Presented by: Vadim S Koshkin, MD, Assistant Professor of Hematology and Oncology, Dept. of Medicine at The University of California San Francisco Helen Diller Family Comprehensive Cancer Center

Co-Authors: Yilun Sun, Dory Freeman, Chelsea K. Osterman, Christopher Su, Divya Natesan, Ali Raza Khaki, Dimitrios Makrakis, Jayanshu Jain, Anders Olsen, Arnab Basu, Pedro C. Barata, Yousef Zakharia, Mehmet Asim Bilen, Hamid Emamekhoo, Nancy B. Davis, Matthew I. Milowsky, Deepak Kilari, Guru Sonpavde, Ajjai Shivaram Alva

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Twitter @WallisCJD during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021