Pembrolizumab Plus Gemcitabine-Platinum Doublet Chemotherapy Improves Survival Regardless of Platinum Agent for Urothelial Carcinoma

According to subset analysis results from the phase 3 KEYNOTE-361 study, the addition of pembrolizumab to gemcitabine-platinum doublet chemotherapy improved survival compared to gemcitabine-platinum doublet chemotherapy alone among patients with advanced or metastatic urothelial carcinoma, regardless of platinum agent choice. 

“Until recently, the standard first-line treatment for advanced urothelial carcinoma included platinum-based chemotherapy containing either cisplatin or carboplatin,” stated Thomas Powles, MD, Barts Cancer Center, London, United Kingdom, and coauthors. Here researchers aim “to determine if there are differences in clinical benefit between patients who received cisplatin-based versus carboplatin-based combination therapy.” 

For this analysis, 1010 patients were randomized on a 1-to-1-to-1 basis to receive 200 mg of pembrolizumab every 3 weeks for ≤ 35 cycles with or without chemotherapy, or chemotherapy alone. There were 703 patient total assigned to receive a chemotherapy-containing regimen of gemcitabine plus investigator’s choice cisplatin (n = 312) or carboplatin (n = 391). Primary end points included progression-free survival (PFS) and objective response rate (ORR) via blinded independent central review. Overall survival (OS) was assessed among patients assigned to receive cisplatin- or carboplatin-based chemotherapy with or without pembrolizumab. 

The median follow-up duration was of 31.1 months. Among patients treated with cisplatin-based chemotherapy, the median OS was 20.1 months in the pembrolizumab arm and 16.4 months in the chemotherapy alone arm. Median PFS was 8.5 months in the pembrolizumab arm and 7.1 months in the chemotherapy alone arm and the ORR was 64.1% and 48.7%, respectively. Among patients treated with carboplatin-based chemotherapy, median OS was 15.5 months in the pembrolizumab arm and 12.3 months in the chemotherapy alone arm. Median PFS was 8 months in the pembrolizumab arm and 6.7 months in the chemotherapy alone arm and the ORR was 47.2% and 41.8%, respectively. 

In the cisplatin-based arm 55.8% of patients received subsequent anti-PD-L1 therapy, compared to 41.8% of patients in the carboplatin-based arm. Pembrolizumab did not increase the incidence of adverse events. 

As Dr Powles et al concluded, “Results suggest trends towards OS and PFS improvements with the addition of pembrolizumab to gemcitabine-platinum doublet over gemcitabine-platinum alone regardless of whether cisplatin or carboplatin was the chosen platinum agent.” 

Source: 

Powles T, Csoszi T, Loriot Y, 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. Published online: November 1, 2024. doi: 10.1016/j.clgc.2024.102261