Pembrolizumab Monotherapy Demonstrates Clinical Efficacy in High-risk NMIBC


Treatment with pembrolizumab monotherapy resulted in stable long-term disease-free survival rates in patients with Bacillus Calmette-Guérin–unresponsive, high-risk non–muscle-invasive bladder cancer.

Eric A. Singer, MD

Eric A. Singer, MD

Treatment with pembrolizumab monotherapy resulted in stable long-term disease-free survival (DFS) rates in patients with Bacillus Calmette-Guérin (BCG)–unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC), according to primary findings from the phase 2 KEYNOTE-057 trial (NCT02625961) presented at the 2023 American Urological Association Annual Meeting.1

The results were specifically for patients from cohort B of KEYNOTE-057, which included patients with BCG-unresponsive high-risk NMIBC with non-CIS papillary tumors only (high-grade Ta or any-grade T1) at baseline. Patients were either ineligible for or declined to undergo radical cystectomy.

At a median follow-up of 45.4 months (range, 14.9-77.1) for cohort B, the 12-month DFS rate was 43.5% (95% CI, 34.9%-51.9%). The median DFS was 7.7 months (95% CI, 5.5-13.6).

“Of note, at 24 and 36 months, DFS rate remained stable at about 35%,” said presenting author Eric A. Singer, MD, professor of Urology and Bioethics, director of the Division of Urologic Oncology, The Ohio State University Wexner Medical Center and The Ohio State University Comprehensive Cancer Center.

Overall, cohort B included 132 patients with a median age of 72 years (range, 37-87), 104 (78.8%) of whom were male. Regarding tumor stage, 43% (n = 57) of patients had T1 disease at baseline and 57% (n = 75) of patients had high-grade Ta disease. The median number of prior BCG instillations was 10 (range, 6-33).

“With 132 patients and about 45 months of follow-up, KEYNOTE-057 cohort B is among the most robust data sets for nonsurgical therapy in patients with papillary high-risk NMIBC,” said Singer.

Pembrolizumab was dosed at 200 mg every 3 weeks for a maximum of 35 cycles (about 2 years). The primary end point was the 12-month DFS rate.

“Unfortunately, not every patient had a durable complete response, and approximately half of patients ended up requiring some additional type of therapy after discontinuing pembrolizumab,” said Singer.

Specifically, there were 36 (27%) patients who subsequently received a radical cystectomy. Of this group, only 4 patients were upstaged to MIBC at the time of radical cystectomy.

“Low rates of upstaging at the time of radical cystectomy are consistent with…previous reports of patients who undergo immediate radical cystectomy upon BCG failure, suggesting that the window for subsequent curative intent radical cystectomy is generally preserved despite a lack of response to pembrolizumab [in these patients],” said Singer.

Safety data showed that 73.5% of patients experienced at least 1 treatment-related adverse event (TEAE). Grade 3/4 TEAEs occurred in 14.4% of patients. There were no patient deaths related to TEAEs.

Singer noted that quality-of-life measures were “stable or improved for most patients during treatment.”

Results were previously reported from cohort A of KEYNOTE-057, which consisted of patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.2 The clinical CR rate with pembrolizumab in cohort A was 41% at 3 months. The median duration of CR was 16.2 months. Based on these data, the FDA approved pembrolizumab in January 2020 for use in this patient population.


  1. Singer E, Necchi A, Roumiguié M, et al. Pembrolizumab (PEMBRO) for patients (PTS) with high-risk non-muscle-invasive bladder cancer (HR NMIBC) unresponsive to bacillus calmette-guerin (BCG): efficacy and evaluation of subsequent cystectomy from cohort B of the phase 2 KEYNOTE-057 study. Presented at 2023 AUA Annual Meeting. April 27-May 1, 2023; Chicago, IL. Abstract LBA03-08. doi: 10.1097/JU.0000000000003426.08
  2. Balar AV, Kamat AM, Kulkarni GS, 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;22(7):919-930. doi:10.1016/S1470-2045(21)00147-9
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