Somatic alterations of and associated with response to enfortumab vedotin in patients with advanced urothelial cancer.
Tanya Jindal, Xiaolin Zhu, Rohit Bose, Vipul Kumar, Edward Maldonado, Prianka Deshmukh, Chase Shipp, Stephanie Feng, Michelle S Johnson, Austin Angelidakis, Daniel Kwon, Hala T Borno, Ivan de Kouchkovsky, Arpita Desai, Rahul Aggarwal, Lawrence Fong, Eric J Small, Anthony Wong, Sima Porten, Jonathan Chou, Terence Friedlander, Vadim S Koshkin
Author Information
Tanya Jindal: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Xiaolin Zhu: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Rohit Bose: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Vipul Kumar: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Edward Maldonado: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Prianka Deshmukh: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Chase Shipp: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Stephanie Feng: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Michelle S Johnson: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Austin Angelidakis: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Daniel Kwon: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Hala T Borno: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Ivan de Kouchkovsky: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Arpita Desai: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Rahul Aggarwal: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Lawrence Fong: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Eric J Small: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Anthony Wong: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Sima Porten: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Jonathan Chou: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Terence Friedlander: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Vadim S Koshkin: Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, United States.
Background: Enfortumab vedotin (EV) is an antibody-drug conjugate approved for patients with treatment-refractory advanced urothelial carcinoma (aUC), however data on biomarkers of response is lacking. Methods: We retrospectively identified all aUC patients at our institution who received EV monotherapy and had next-generation sequencing (NGS) data available. Patients were considered responders if they had a complete response or partial response on restaging scans during treatment. Observed response rate (ORR) was evaluated by local investigator and compared between responders and non-responders using Chi-squared test. A univariable analysis was conducted using the Cox proportional hazard test to assess for associations between baseline characteristics and most common somatic alterations (in ≥10% of patients) with patient survival outcomes [progression-free survival (PFS) and overall survival (OS)]. Somatic alterations were then individually evaluated in separate multivariate models while accounting for patient and clinical characteristics using Cox regression models. Results: Among 29 patients treated with EV monotherapy, 27 had available NGS data. Median age was 70, 24 (83%) were men, 19 (62%) were Caucasian, 15 (52%) had pure urothelial histology and 22 (76%) had primary tumor in the bladder. ORR was 41%, and PFS and OS for the overall cohort were 5.1 months and 10.2 months. Responders were enriched among patients with and alterations. Patients with these alterations, as well as those with composite alterations (alterations in either or ), also had increased ORR with EV treatment compared to patients without these alterations. In the univariable analysis, baseline albumin level ≥ 3.0g/dL and presence of composite alterations were associated with a prolonged OS. Baseline ECOG 0/1, alterations and alterations were associated with a prolonged PFS. In the multivariable analysis, and alterations were genomic markers predictive of improved PFS after accounting for the relevant clinical characteristics. Conclusion: In this single-center retrospective analysis of aUC patients treated with EV, presence of or somatic alterations, lower ECOG PS scores (ECOG 0 or 1) and higher albumin levels (≥3 g/dL) were associated with improved outcomes with EV treatment. Prospective and external validation of these findings in larger cohorts is warranted.
