Enfortumab vedotin合併Pembrolizumab應用於泌尿上皮癌做為前導性治療之初步結果

張家郡¹、吳錫金^1,2,3、楊啟瑞¹、蔡禮賢¹、張兆祥^1,2

¹中國醫藥大學附設醫院 泌尿部；²中國醫藥大學 醫學系；³中國醫藥大學北港附設醫院泌尿科

Preliminary results of Neoadjuvant therapy with Enfortumab vedotin and Pembrolizumab in urothelial carcinoma patients

Jia-Jyun Jhang¹, Hsi-Chin Wu^1,2,3, Chi-Rei Yang¹, Li-Hsien Tsai¹, Chao-Hsiang Chang^1,2

¹Department of Urology, China Medical University Hospital, Taichung, Taiwan; ² School of Medicine, China Medical University, Taichung, Taiwan; ³Department of Urology, China Medical University Beigang Hospital, Yunlin, Taiwan

Purpose: Enfortumab vedotin(EV), an antibody-drug conjugate (ADC) targeting nectin-4 combined with Pembrolizumab is now the standard first-line therapy for advanced urothelial carcinoma (UC) patients, as recent trial demonstrate an outstanding response rate with the combination. We aim to evaluate the effectiveness of EV and pembrolizumab as a neoadjuvant treatment in UC patients

Materials and Methods: We conducted a retrospective study of patients with urothelial carcinoma (UC) who received neoadjuvant treatment with EV and pembrolizumab between October 2023 and November 2024 at China Medical University Hospital. Patients who did not undergo subsequent operation were excluded. The study focused on the rate of pathological downstaging, tumor-free survival, adverse events (AEs) related to systemic therapy, and surgical complications. Surgical complications were classified using the Clavien-Dindo grading system, and drug toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE).

Results: Our study included 7 patients (3 males and 4 females): 4 with bladder UC and 3 with upper tract UC. All patients received neoadjuvant therapy on a 3-weeks cycle of EV 60mg on day 1, day 8 and Pembrolizumab 200mg on day 1. Patients averagely received 4.1 cycles prior to operation. Pathological down staging was observed in 6 patients (85.7%), complete pathological response was achieved in 3 patients (42.9%). During a median follow up interval of 9.7 months, no patient experienced disease recurrence. Grade 3 or higher surgical complication occurred in only 1 patient (14.2%). Grade 3 or higher-grade AEs were just observed in 1 patient (14.2%). No treatment-related complications that resulted in death or discontinuation of systemic therapy.

Conclusions: Our study demonstrates that the combination of EV and Pembrolizumab may offer satisfactory peri-operative outcome with manageable AEs. The high rates of complete response and pathological down staging align with the previously observed high objective response rates in trials for advanced-stage UC. Further studies are needed to determine the optimal dosage and treatment intervals for this combination.