Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible...

Area of Science:

• Oncology
• Immunotherapy
• Urothelial Carcinoma Research

Background:

• Advanced urothelial carcinoma (UC) presents significant treatment challenges, especially for patients ineligible for cisplatin-based chemotherapy.
• First-line treatment options for this patient population are critical for improving outcomes.

Purpose of the Study:

• To evaluate the efficacy and safety of first-line pembrolizumab in patients with locally advanced or metastatic cisplatin-ineligible urothelial carcinoma (UC).
• To assess objective response rate (ORR), duration of response, and overall survival (OS) in this cohort.

Main Methods:

• The phase II KEYNOTE-052 study enrolled 370 cisplatin-ineligible UC patients receiving pembrolizumab 200 mg every 3 weeks.
• Response was assessed by independent central review; programmed death ligand 1 (PD-L1) expression was defined by combined positive score (CPS) ≥ 10.

Main Results:

• The overall objective response rate (ORR) was 28.6%, with a median duration of response of 30.1 months.
• Median overall survival (OS) was 11.3 months; 24-month OS rate was 31.2%.
• In patients with PD-L1 CPS ≥ 10, ORR was 47.3% and median OS was 18.5 months. Patients with lymph node-only disease showed an ORR of 49.0% and median OS of 27.0 months.

Conclusions:

• First-line pembrolizumab provides meaningful and durable clinical responses in cisplatin-ineligible advanced UC patients.
• Pembrolizumab treatment is associated with prolonged OS, especially in patients with PD-L1 CPS ≥ 10 and those with lymph node-only disease.