A RECENT study has investigated the efficacy of first-line pembrolizumab, with or without platinum-based chemotherapy, compared to chemotherapy alone in patients with advanced or metastatic urothelial carcinoma. The study’s primary endpoints of progression-free survival (PFS) and overall survival (OS) were not met. However, an exploratory analysis examined the efficacy of pembrolizumab in combination with either cisplatin- or carboplatin-based chemotherapy.
A total of 1,010 patients were enrolled, with 703 receiving a chemotherapy-containing regimen. Of these, 312 received cisplatin-based chemotherapy, while 391 received carboplatin-based chemotherapy. Patients were randomly assigned to receive pembrolizumab with chemotherapy or chemotherapy alone. The analysis evaluated PFS, objective response rate (ORR) per RECIST v1.1, and OS based on the choice of platinum agent.
For patients receiving cisplatin-based chemotherapy, the median OS was 20.1 months with pembrolizumab compared to 16.4 months without (HR 0.88, 95% CI, 0.67–1.15). The median PFS was 8.5 months with pembrolizumab versus 7.1 months without (HR 0.67, 95% CI, 0.51–0.89). ORR was 64.1% in the pembrolizumab arm compared to 48.7% in the chemotherapy-alone arm. Among patients receiving carboplatin-based chemotherapy, median OS was 15.5 months with pembrolizumab versus 12.3 months without (HR 0.84, 95% CI, 0.67–1.06). Median PFS was 8.0 months with pembrolizumab and 6.7 months with chemotherapy alone (HR 0.86, 95% CI, 0.68–1.09). ORR was 47.2% versus 41.8%, respectively.
Notably, a greater proportion of patients in the cisplatin-based chemotherapy-alone arm (55.8%) received subsequent anti-programmed cell death protein 1/ligand 1 (PD-1/PD-L1) therapy compared to those in the carboplatin-based chemotherapy-alone arm (41.8%), which may have influenced OS outcomes. The addition of pembrolizumab did not significantly increase the incidence of adverse events.
Although the primary endpoints were not met, the results suggest trends towards OS and PFS improvements with pembrolizumab in combination with platinum-based chemotherapy, regardless of whether cisplatin or carboplatin was used. The potential impact of subsequent therapies on OS highlights the complexity of interpreting survival outcomes in this setting. Further research is needed to clarify the role of pembrolizumab in first-line treatment for advanced urothelial carcinoma.
Katie Wright, EMJ
Reference
Powles T et al. Cisplatin- or carboplatin-based chemotherapy plus pembrolizumab in advanced urothelial cancer: exploratory analysis from the Phase 3 KEYNOTE-361 study. Clin Genitourin Cancer. 2025;23(1):102261.
