TY - JOUR
T1 - Re-challenging chemotherapy after pembrolizumab in platinum-refractory urothelial carcinoma
AU - Uchimoto, Taizo
AU - Fukushima, Tatsuo
AU - Komura, Kazumasa
AU - Fukuokaya, Wataru
AU - Adachi, Takahiro
AU - Hashimoto, Takeshi
AU - Yoshizawa, Atsuhiko
AU - Nakamura, Ko
AU - Yano, Yusuke
AU - Nishimura, Kazuki
AU - Nishio, Kyosuke
AU - Nakamori, Keita
AU - Iwatani, Kosuke
AU - Yamamoto, Shutaro
AU - Urabe, Fumihiko
AU - Mori, Keiichiro
AU - Yanagisawa, Takafumi
AU - Tsuduki, Shunsuke
AU - Takahara, Kiyoshi
AU - Inamoto, Teruo
AU - Miki, Jun
AU - Kimura, Takahiro
AU - Ohno, Yoshio
AU - Shiroki, Ryoichi
AU - Egawa, Shin
AU - Azuma, Haruhito
N1 - Funding Information:
This study was partially supported by Grant‐in‐Aid No. 21H03070 (Japan Society for the Promotion of Science), the Osaka Medical Research Foundation for Intractable Disease, and the Takeda Science Foundation in Japan.
Publisher Copyright:
© 2022 BJU International.
PY - 2022
Y1 - 2022
N2 - Objectives: To assess the real-world clinical benefit of re-challenging chemotherapy after pembrolizumab in patients with metastatic urothelial carcinoma (mUC), as there have been several reports suggesting that programmed cell death protein-1/programmed death-ligand 1inhibitors can restore platinum sensitivity. Patients and Methods: Of 236 patients treated with pembrolizumab, we excluded 45 patients who did not experience progressive disease (PD) for pembrolizumab during the follow-up and 86 patients who discontinued pembrolizumab by the diagnosis of PD followed by the best supportive care. A total of 105 patients were identified for a logistic regression propensity score model to compare the survival outcomes between patients treated with continuing pembrolizumab (80) and re-challenging chemotherapy (25) after the diagnosis of PD for pembrolizumab. Results: A median overall survival (OS) from PD for pembrolizumab was 11 months in 105 patients. Of 25 patients treated with re-challenging chemotherapy, platinum-including chemotherapy (gemcitabine and cisplatin; gemcitabine/cisplatin/paclitaxel [GCP]; methotrexate and vinblastine and adriamycin and cisplatin; and methotrexate and carboplatin and vinblastine MCAVI) was offered in 20 patients (80%). The objective response rate (ORR) for the first-line chemotherapy in the 105 patients was 30%, with a comparable ORR in 25 patients treated with re-challenging chemotherapy of 28%. GCP as a re-challenging regimen was offered in 12 of 25 (48%) patients. The ORR for the GCP regimen was 50%. Propensity score matching was performed using putative clinical factors, from which 34 patients were identified as pair-matched groups. The OS for patients treated with re-challenging chemotherapy was significantly longer than continuing pembrolizumab (a median of 13.9 and 5.8 months, respectively: P = 0.048). Conclusion: Re-challenging chemotherapy including platinum agents after PD with pembrolizumab offers clinical benefits in patients with mUC.
AB - Objectives: To assess the real-world clinical benefit of re-challenging chemotherapy after pembrolizumab in patients with metastatic urothelial carcinoma (mUC), as there have been several reports suggesting that programmed cell death protein-1/programmed death-ligand 1inhibitors can restore platinum sensitivity. Patients and Methods: Of 236 patients treated with pembrolizumab, we excluded 45 patients who did not experience progressive disease (PD) for pembrolizumab during the follow-up and 86 patients who discontinued pembrolizumab by the diagnosis of PD followed by the best supportive care. A total of 105 patients were identified for a logistic regression propensity score model to compare the survival outcomes between patients treated with continuing pembrolizumab (80) and re-challenging chemotherapy (25) after the diagnosis of PD for pembrolizumab. Results: A median overall survival (OS) from PD for pembrolizumab was 11 months in 105 patients. Of 25 patients treated with re-challenging chemotherapy, platinum-including chemotherapy (gemcitabine and cisplatin; gemcitabine/cisplatin/paclitaxel [GCP]; methotrexate and vinblastine and adriamycin and cisplatin; and methotrexate and carboplatin and vinblastine MCAVI) was offered in 20 patients (80%). The objective response rate (ORR) for the first-line chemotherapy in the 105 patients was 30%, with a comparable ORR in 25 patients treated with re-challenging chemotherapy of 28%. GCP as a re-challenging regimen was offered in 12 of 25 (48%) patients. The ORR for the GCP regimen was 50%. Propensity score matching was performed using putative clinical factors, from which 34 patients were identified as pair-matched groups. The OS for patients treated with re-challenging chemotherapy was significantly longer than continuing pembrolizumab (a median of 13.9 and 5.8 months, respectively: P = 0.048). Conclusion: Re-challenging chemotherapy including platinum agents after PD with pembrolizumab offers clinical benefits in patients with mUC.
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U2 - 10.1111/bju.15893
DO - 10.1111/bju.15893
M3 - Article
C2 - 36098556
AN - SCOPUS:85138703394
JO - British Journal of Urology
JF - British Journal of Urology
SN - 1464-4096
ER -