Pembrolizumab in High-Risk Non–Muscle-Invasive Bladder Cancer

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As reported in The Lancet Oncology by Andrea Necchi, MD, and colleagues, findings in cohort B of the phase II KEYNOTE-057 study indicated that pembrolizumab was active in patients with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non–muscle invasive bladder cancer. 

As noted by the investigators, “In cohort A (patients with carcinoma in situ, with or without papillary tumors) of the KEYNOTE-057 study, pembrolizumab monotherapy led to a complete response rate of 41% at 3 months, and 46% of responders maintained a response lasting at least 12 months.”

Andrea Necchi, MD

Andrea Necchi, MD

Study Details

In cohort B of the trial, 132 patients with papillary tumors (high-grade Ta or any-grade T1) without carcinoma in situ who had received a median of 10 (interquartile range [IQR] = 9–15) BCG instillations and who declined or were ineligible for radical cystectomy were enrolled from sites in 14 countries between 2016 and 2021.

Patients received pembrolizumab at 200 mg every 3 weeks for a maximum of 35 cycles. Transurethral resection of the bladder tumor within 12 weeks of the first pembrolizumab dose was required.

The primary outcome measure of the trial was 12-month disease-free survival.

Disease-Free Survival

At data cutoff in October 2022, median follow-up was 45.4 months (IQR = 36.4–59.3 months). Disease-free survival at 12 months was 43.5% (95% confidence interval [CI] = 34.9%–51.9%). Median disease-free survival was 7.7 months (95% CI = 5.5–13.6 months). Among patients with a PD-L1 combined positive score (CPS) ≥ 10, 12-month disease-free survival was 54.1% (95% CI = 36.9%–68.4%). Among those with a PD-L1 CPS < 10, 12-month disease-free survival was 39.4% (95% CI = 29.4%–49.2%).

Median progression-free survival to worsening of grade, stage, or death was 44.5 months (95% CI = 34.6% to not reached). Median overall survival was not reached.


  • Disease-free survival at 12 months was 43.5%.
  • Rates were 54.1% vs 39.4% among patients with PD-L1 CPS ≥ 10 vs < 10, respectively.

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in 14% of patients, most commonly colitis (in 2%) and diarrhea (in 2%). Serious treatment-related adverse events occurred in 13% of patients, most commonly colitis (in 2%). Treatment-related adverse events led to discontinuation of treatment in 11% of patients. No treatment-related deaths were reported.

The investigators concluded, “Pembrolizumab monotherapy showed antitumor activity and manageable toxicity in patients with BCG-unresponsive high-risk Ta or T1 bladder cancer without carcinoma in situ and could potentially be a suitable treatment option for patients who decline or are ineligible for radical cystectomy. Findings will need to be confirmed in a randomized controlled trial.”

Dr. Necchi, of Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Merck Sharp & Dohme. For full disclosures of the study authors, visit

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