Pembrolizumab for Bladder Cancer: An Overview

Urothelial carcinoma - the most common form of bladder cancer - has historically been treated with platinum-based chemotherapy in the advanced or metastatic setting. Pembrolizumab has added a significant option for patients either ineligible for chemotherapy or who have progressed through it, with evidence spanning two major clinical settings.

The two main settings for pembrolizumab in bladder cancer

Pembrolizumab is used in urothelial carcinoma in two distinct clinical situations. The first is as first-line treatment for patients who are not suitable for cisplatin-based chemotherapy - a group that includes many older patients or those with reduced kidney function. The second is as second-line treatment after a platinum-based chemotherapy regimen has been tried and the disease has progressed.

KEYNOTE-052: Cisplatin-ineligible patients

KEYNOTE-052 evaluated pembrolizumab monotherapy as first-line treatment for patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin. The overall response rate was approximately 29%, with around 7% of patients achieving a complete response. Importantly, many responses were durable - persisting for over a year in a meaningful proportion of responders. For patients who cannot tolerate cisplatin and previously had no effective first-line option, this represented a significant advance.

KEYNOTE-045: Second-line treatment after platinum chemotherapy

KEYNOTE-045 compared pembrolizumab to chemotherapy (investigator's choice of paclitaxel, docetaxel, or vinflunine) in patients whose urothelial carcinoma had progressed after platinum-based treatment. Pembrolizumab produced a significantly longer overall survival (10.3 months vs 7.4 months) and, critically, a substantially better tolerability profile. The reduction in grade 3-4 toxicity with pembrolizumab compared to chemotherapy was clinically meaningful, particularly for patients who had already been through a course of platinum treatment.

PD-L1 and bladder cancer eligibility

PD-L1 testing in urothelial carcinoma uses the Combined Positive Score (CPS). In the cisplatin-ineligible first-line setting, CPS 10 or higher was associated with higher response rates, but pembrolizumab is used more broadly given the limited alternatives. In the second-line setting, benefit was seen regardless of PD-L1 expression. An oncologist will review your PD-L1 status alongside your treatment history to advise on the most appropriate approach.