AUA 2023: Pembrolizumab for Patients With High-Risk Non-Muscle-Invasive Bladder Cancer Unresponsive to Bacillus Calmette-Guerin : Efficacy and Evaluation of Subsequent Cystectomy From Cohort B of the Phase 2 KEYNOTE-057 Study

( During the 2023 American Urological Association’s Late Breaking Abstract III - Cancer session, Dr. Eric Singer presented results from cohort B of the phase 2 KEYNOTE-057 study. KEYNOTE-057 is a multicohort study investigating the safety and efficacy of pembrolizumab monotherapy in patients with BCG-unresponsive HR NMIBC who were ineligible for or declined radical cystectomy (RC). Cohort A, which consisted of patients with CIS +/- papillary tumors, demonstrated a complete response (CR) rate of 41% at 3 months, with a median duration of CR of 16 months, which led to FDA approval.

In this presentation, Dr. Singer presented results from Cohort B, which consisted of patients with papillary tumors only, without CIS. Median follow up was 45.4 months, and the cohort included patients who underwent eventual RC. The authors hypothesized that pembrolizumab monotherapy would result in a 12-month disease-free survival (DFS) rate of high risk non-muscle invasive bladder cancer (HR NMIBC) >20%.

Study schema is noted below – patients received 200 mg IV pembrolizumab for ≤35 cycles, approximately a 2 year period. Primary outcome was 12-month DFS rate of HR NMIBC, and secondary endpoints included 12-months DFS of any disease, time to RC, and pathologic staging at RC.


In total, 132 patients were enrolled, with a median of 10 prior BCG instillations (range: 6 – 22). Of those patients, 57 (43.2%) had T1 NMIBC, and 75 (56.8%) had HGTa NMIBC. The primary outcome, 12-month DFS rate of HR NMIBC was 43.5% (95% CI, 34.9-51.9), while the DFS rate of any disease was 41.7% (33.1-50.0) at one year.

disease free

Dr. Singer then reviewed safety data: 97 patients (73.5%) experienced adverse events (AE) related to treatment, with 19 patients (14.4%) experiencing a grade 3 or 4 treatment-related AE. No deaths from treatment-related AEs were reported.

treatment related aes

Next, he discussed subsequent therapy after study treatment: 36 patients (28.3%) underwent RC after cessation of pembrolizumab. Of those, 8 patients (18.6%) achieved initial disease-free status.

study treatment

time to radical cystectomy

Dr. Singer proceeded to conclude his presentation with the following points:

  • In Cohort B, consisting of 132 patients and about 45 months of follow up, this study provides some of the most robust data for nonsurgical therapy in patients with papillary HR NMIBC
  • DFS was maintained in >1/3 of patients with BCG-unresponsive disease at 3 years after pembrolizumab monotherapy
  • Consistent with prior studies, safety was manageable without any new signals, and no treatment-related deaths
    • Quality of life measures were stable or improved for most patients
  • Even in patients who underwent eventual RC, there were low rates of upstaging. This is consistent with Cohort A data (CIS patients) and prior studies of patients who undergo upfront RC upon BCG failure.
    • This suggests that the window for curative intent RC is preserved, despite the lack of response to pembrolizumab

Presented By: Eric Singer, MD, MA, MS, FACS, FASCO, The Ohio State University School of Medicine, Columbus, OH

Written By: Ruchika Talwar, MD, Urologic Oncology Fellow, Vanderbilt University Medical Center, during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023

  1. Balar AV et al. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 2021
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