Pembrolizumab Remains Effective for Years in a Bladder Cancer Subset

Long-term follow-up showed that the use of pembrolizumab monotherapy maintained durable complete responses, while rates of upstaging at the time of radical cystectomy were consistent with previous findings in the KEYNOTE-057 trial in patients with a bladder cancer subset.

Patients with bacillus Calmette-Geurin (BCG)-unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC) and carcinoma in situ with or without papillary disease continue to derive benefit from pembrolizumab (Keytruda) monotherapy, according to 5-year follow-up results from the KEYNOTE-057 trial (NCT02625961) presented at the 2022 Society of Urologic Oncology Annual Meeting.1

“The long-term efficacy data continue to support the use of pembrolizumab monotherapy in patients with BCG-unresponsive, [high-risk] NMBIC and [carcinoma in situ],” the investigators wrote in their poster presentation.

Further, among those who did not experience a CR, rates of upstaging at the time of radical cystectomy were consistent with previous findings, “suggesting that the window of opportunity for subsequent radical cystectomy is largely preserved,” the investigators added.

Although transurethral resection of bladder tumor (TURBT) followed by intravesical BCG is the current standard of care for this patient population, half of these patients’ disease goes on to recur or progress, the investigators wrote. Therefore, in the trial, 96 evaluable patients received 200 mg pembrolizumab intravenously every 3 weeks for up to 24 months or until centrally confirmed disease persistence, recurrence, or progression; unacceptable toxic effects; or withdrawal of consent.

In cohort A of the open-label, single-arm, multicenter phase 2 KEYNOTE-057 trial, investigators evaluated the efficacy and safety of pembrolizumab in patients with BCG-unresponsive, high-risk NMIBC and carcinoma in situ, with or without papillary disease, who were ineligible for or decline to receive radical cystectomy—the current standard of care for this patient population.

Cohort A was comprised of adults aged 18 years or older with histologically confirmed BCG-unresponsive carcinoma in situ of the bladder, with or without papillary tumors, with an Eastern Cooperative Oncology Group performance status of 0–2, and who were ineligible for or declined radical cystectomy.

Clinical complete response rate served as the primary end point.

Initial findings demonstrated, after a median follow-up of 36.4 months, that 40.6% of patients experienced a CR at 3 months (95% CI, 30.7%-51.1%).

Duration of response among patients with a CR (n = 39) was 16.2 months (range, 0.0+ to 57.7+).

The Kaplan-Meier estimated overall survival (OS) among all participants was 27.1%, with median OS not reached (NR; 95% CI, NR-NR).

Following pembrolizumab discontinuation, 43 patients went on to receive subsequent radical cystectomy. The median time from first dose of pembrolizumab to radical cystectomy was 9 months (range, 4.0-41.8 months) in all patients who underwent radical cystectomy. In particular, the median time from first dose of pembrolizumab to radical cystectomy was 14.3 months (range, 9.0-32.5 months) for 12 patients with a CR who later experienced disease recurrence or progression, and 6.4 months (range, 4.0-41.8 months) in 31 patients without a CR.

Among the patients who underwent radical cystectomy, 5 progressed to muscle-invasive bladder cancer.

Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 13 (13%) patients, the most common being arthralgia (2%) and hyponatraemia (3%). Serious TRAEs occurred in 8 (8%) patients, but there were no deaths that were considered treatment related.2

Data cutoff for the 5-year follow-up was May 15, 2022. Of the 96 patients treated in the original study, 38 patients had persistent disease, 33 had progressive disease, 8 discontinued because of adverse events (AEs), 4 patients discontinued because of CR, 3 patients withdrew from the study, 1 patient experienced clinical progression, and 1 patient was not compliant with the study drug.

The median time from first dose data cutoff was 60.4 months (range, 50.2-72.5 months).

To conclude, the investigators noted that “analysis of long-term safety results for both cohorts A and B are forthcoming.”


1. Kulkarni GS, Kamat AM, Uchio EM, et al. Pembrolizumab in participants with bacillus calmette-geurin-unresponsive non-muscle invasive bladder cancer: 5-year follow-up from cohort A of the phase 2 KEYNOTE-057 Trial. Presented at: Society of Urologic Oncology 23rd Annual Meeting; November 30-December 2, 2022; San Diego, California. Poster 188.

2. Balar AV, Kamat GS, 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.