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

BJU Int. 2023 Apr;131(4):477-485. doi: 10.1111/bju.15893. Epub 2022 Sep 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Transitional Cell* / pathology
  • Cisplatin / therapeutic use
  • Deoxycytidine / therapeutic use
  • Gemcitabine
  • Humans
  • Methotrexate
  • Platinum / therapeutic use
  • Urinary Bladder Neoplasms* / pathology
  • Urologic Neoplasms* / pathology
  • Vinblastine / therapeutic use


  • Cisplatin
  • pembrolizumab
  • Vinblastine
  • Platinum
  • Methotrexate
  • Gemcitabine
  • Deoxycytidine