Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr;131(4):477-485.
doi: 10.1111/bju.15893. Epub 2022 Sep 26.

Re-challenging chemotherapy after pembrolizumab in platinum-refractory urothelial carcinoma

Taizo Uchimoto  1 , Tatsuo Fukushima  1 , Kazumasa Komura  1 , Wataru Fukuokaya  2 , Takahiro Adachi  3 , Takeshi Hashimoto  3 , Atsuhiko Yoshizawa  4 , Ko Nakamura  1 , Yusuke Yano  1 , Kazuki Nishimura  1 , Kyosuke Nishio  1 , Keita Nakamori  1 , Kosuke Iwatani  2 , Shutaro Yamamoto  2 , Fumihiko Urabe  2 , Keiichiro Mori  2 , Takafumi Yanagisawa  2 , Shunsuke Tsuduki  2 , Kiyoshi Takahara  4 , Teruo Inamoto  1 , Jun Miki  2 , Takahiro Kimura  2 , Yoshio Ohno  3 , Ryoichi Shiroki  4 , Shin Egawa  2 , Haruhito Azuma  1
Affiliations

Re-challenging chemotherapy after pembrolizumab in platinum-refractory urothelial carcinoma

Taizo Uchimoto et al. BJU Int. 2023 Apr.

Abstract

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.

Keywords: objective response; overall survival; pembrolizumab; platinum-refractory; re-challenging chemotherapy; urothelial carcinoma.

PubMed Disclaimer

References

    1. von der Maase H, Hansen SW, Roberts JT et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000; 18: 3068-77
    1. Bellmunt J, de Wit R, Vaughn DJ et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 2017; 376: 1015-26
    1. Fradet Y, Bellmunt J, Vaughn DJ et al. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up. Ann Oncol 2019; 30: 970-6
    1. Powles T, Rosenberg JE, Sonpavde GP et al. Enfortumab Vedotin in previously treated advanced urothelial carcinoma. N Engl J Med 2021; 384: 1125-35
    1. Furubayashi N, Hori Y, Morokuma F et al. Paclitaxel and carboplatin chemotherapy after platinum-based chemotherapy and pembrolizumab for metastatic urothelial carcinoma. Mol Clin Oncol 2021; 14: 91

Publication types

LinkOut - more resources