TY - JOUR
T1 - Durable Response to Enfortumab Vedotin Compared to Re-challenging Chemotherapy in Metastatic Urothelial Carcinoma After Checkpoint Inhibitors
AU - Uchimoto, Taizo
AU - Tsuchida, Shuya
AU - Komura, Kazumasa
AU - Fukuokaya, Wataru
AU - Adachi, Takahiro
AU - Hirasawa, Yosuke
AU - Hashimoto, Takeshi
AU - Yoshizawa, Atsuhiko
AU - Saruta, Masanobu
AU - Hashimoto, Mamoru
AU - Higashio, Takuya
AU - Matsuda, Takuya
AU - Nishimura, Kazuki
AU - Tsujino, Takuya
AU - Nakamura, Ko
AU - Fukushima, Tatsuo
AU - Nishio, Kyosuke
AU - Yamamoto, Shutaro
AU - Iwatani, Kosuke
AU - Urabe, Fumihiko
AU - Mori, Keiichiro
AU - Yanagisawa, Takafumi
AU - Tsuduki, Shunsuke
AU - Takahara, Kiyoshi
AU - Inamoto, Teruo
AU - Miki, Jun
AU - Fujita, Kazutoshi
AU - Kimura, Takahiro
AU - Ohno, Yoshio
AU - Shiroki, Ryoichi
AU - Uemura, Hirotsugu
AU - Azuma, Haruhito
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.
PY - 2024/5
Y1 - 2024/5
N2 - Background: Enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, has been used for patients with metastatic urothelial carcinoma (mUC) after progressing on checkpoint inhibitors (CPIs). Re-challenging chemotherapy with platinum agents and continuing CPIs beyond progressive disease (PD) have often been chosen following PD on CPIs, and several studies indicate favorable treatment effects of re-challenging chemotherapy. There is little evidence for comparing EV and re-challenging chemotherapy in real-world clinical practice. Objective: The aim was to reveal the real-world treatment outcomes of EV, re-challenging chemotherapy, and continuing CPIs beyond PD in mUC patients. Patients and Methods: A multi-institutional dataset of 350 mUC patients treated with CPIs was utilized. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated to compare the treatment arms. Results: One hundred and nine mUC patients were treated with EV with a median follow-up of 6.4 months. The ORR and disease control rate (DCR) were 48% and 70%, respectively. The OS from PD on pembrolizumab exhibited significant differences among the three groups, with a median OS of 8, 14, and 29 months in continuing pembrolizumab beyond PD, re-challenging chemotherapy, and EV, respectively. When comparing the survival outcomes from the initiation of the treatment, there is neither a difference in OS (p = 0.124), PFS (p = 0.936), nor ORR (p = 0.816) between EV and re-challenging chemotherapy. Notably, the DOR in patients who achieved an objective response was significantly longer in the EV group than the re-challenging chemotherapy group (a median of 11 and 5 months, p = 0.049). For OS, the difference was not statistically significant (27 and 11 months in EV and re-challenging chemotherapy, respectively: p = 0.05). Conclusions: A superior effect of EV on patient survival compared to re-challenging chemotherapy and continuing pembrolizumab beyond PD was observed in our real-world analysis, which is attributed to the durable DOR in EV treatment despite the similar ORR to re-challenging chemotherapy.
AB - Background: Enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, has been used for patients with metastatic urothelial carcinoma (mUC) after progressing on checkpoint inhibitors (CPIs). Re-challenging chemotherapy with platinum agents and continuing CPIs beyond progressive disease (PD) have often been chosen following PD on CPIs, and several studies indicate favorable treatment effects of re-challenging chemotherapy. There is little evidence for comparing EV and re-challenging chemotherapy in real-world clinical practice. Objective: The aim was to reveal the real-world treatment outcomes of EV, re-challenging chemotherapy, and continuing CPIs beyond PD in mUC patients. Patients and Methods: A multi-institutional dataset of 350 mUC patients treated with CPIs was utilized. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated to compare the treatment arms. Results: One hundred and nine mUC patients were treated with EV with a median follow-up of 6.4 months. The ORR and disease control rate (DCR) were 48% and 70%, respectively. The OS from PD on pembrolizumab exhibited significant differences among the three groups, with a median OS of 8, 14, and 29 months in continuing pembrolizumab beyond PD, re-challenging chemotherapy, and EV, respectively. When comparing the survival outcomes from the initiation of the treatment, there is neither a difference in OS (p = 0.124), PFS (p = 0.936), nor ORR (p = 0.816) between EV and re-challenging chemotherapy. Notably, the DOR in patients who achieved an objective response was significantly longer in the EV group than the re-challenging chemotherapy group (a median of 11 and 5 months, p = 0.049). For OS, the difference was not statistically significant (27 and 11 months in EV and re-challenging chemotherapy, respectively: p = 0.05). Conclusions: A superior effect of EV on patient survival compared to re-challenging chemotherapy and continuing pembrolizumab beyond PD was observed in our real-world analysis, which is attributed to the durable DOR in EV treatment despite the similar ORR to re-challenging chemotherapy.
UR - https://www.scopus.com/pages/publications/85188915289
UR - https://www.scopus.com/pages/publications/85188915289#tab=citedBy
U2 - 10.1007/s11523-024-01047-y
DO - 10.1007/s11523-024-01047-y
M3 - Article
C2 - 38546942
AN - SCOPUS:85188915289
SN - 1776-2596
VL - 19
SP - 401
EP - 410
JO - Targeted Oncology
JF - Targeted Oncology
IS - 3
ER -
