ASCO 2021: First-Line Pembrolizumab (Pembro) in Cisplatin-Ineligible Patients with Advanced Urothelial Cancer (UC): Response and Survival Results up to Five Years from the KEYNOTE-052 Phase 2 Study

( The KEYNOTE-052 study led to the approval of pembrolizumab for the first-line treatment of cisplatin-ineligible patients with advanced urothelial carcinoma. In this presentation, Dr. Peter O’Donnell presented updated results of 5 years of follow-up, with the median time from enrollment to data cutoff of 56.3 months.

The study design, eligibility, and monitoring plan of KEYNOTE-052 are shown below. The primary endpoint of this study was response rate.


Of the 370 patients who started treatment, 11.9% or 44 patients were able to complete the full two years of pembrolizumab treatment. Of the 326 patients who discontinued therapy, 60% discontinued because of disease progression, 17% because of an immune-related adverse event, and 3% were discontinued early because of a complete response.

Patient baseline characteristics are shown below.


Updated overall survival data demonstrate a median overall survival of 11.3 months (95% CI 9.7-13.1). Patients with evidence of higher PD-L1 expression as assessed by a combined positive score greater than or equal to 10 had a longer median overall survival of 18.5 months relative to low PD-L1 expressing tumors at 9.7 months. Patients whose best response to therapy was a complete response had a median overall survival that has not yet been reached, whereas patients whose best response was a partial response had a median survival of 35.9 months. Complete or partial responders did not appear to have drastically different overall survival when stratified by PD-L1 expression. The overall response numbers are summarized below.


Regarding radiographic response of target lesions, 58% experienced any decrease in target lesion size, 41% had a target lesion reduction of more than 30% and 27% had a target lesion reduction of more than 60%. Patients with higher PD-L1 expression were more likely to have a reduction in target lesion size.


The median duration of response was 33.4 months, and when stratified by PD-L1 expression, was 21.2 for low PD-L1 expressing tumors. The median duration of response was not reached for PD-L1 high tumors.

Updated adverse event data is shown below.


Dr. O’Donnell concluded his presentation by discussing that first-line pembrolizumab monotherapy continued to show durable anti-tumor activity 5 years after the last patient was enrolled on study, with a response rate of 28.9%, median duration of response of 33.4 months, and a median overall survival of 11.3 months. Patients with high PD-L1 expression as assessed by CPS score of ten or greater were more likely to respond and have longer responses. No new safety signals emerged. Together these data continue to support clinical benefit for patients from the use of pembrolizumab as first-line therapy for cisplatin-ineligible patients with advanced urothelial carcinoma.

Presented by: Peter H. O’Donnell, MD, The University of Chicago, Chicago, IL

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021
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