In a phase 2 study, pembrolizumab demonstrated antitumor activity in patients with high-risk, papillary non-muscle invasive bladder cancer (NMIBC) who declined or were ineligible for radical cystectomy and whose disease did not respond to Bacillus Calmette-Guérin (BCG).

This patient population has very limited conventional therapies or clinical trial options and represents an unmet medical need, according to study investigator Andrea Necchi, MD, of Vita-Salute San Raffaele University in Milan, Italy.

Dr Necchi presented the study results at the 2023 ASCO Genitourinary Cancers Symposium. The results come from cohort B of the phase 2 KEYNOTE-057 trial ( Identifier: NCT02625961).

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The cohort consisted of 132 NMIBC patients who had papillary tumors without carcinoma in situ, had BCG-unresponsive disease, and had declined or were ineligible for radical cystectomy. At baseline, the median age was 72 (range, 37-87) years, and 79% of patients were men. Patients had received a median of 10 installations of BCG. More patients had high-grade Ta disease (57%) than T1 disease (43%).

All patients received pembrolizumab at 200 mg intravenously every 3 weeks for up to 35 cycles or until disease persistence, recurrence, progression, or unacceptable toxicity. The median follow-up was 45.4 months.

The median disease-free survival (DFS) for high-risk NMIBC was 7.7 months. The DFS rate was 43.5% at 12 months and 34.9% at both 24 months and 36 months. The median DFS was 6.0 months for any disease (defined as low-grade Ta, high-risk disease, and progressive disease). This DFS rate was 41.7% at 12 months and 33.0% at both 24 months and 36 months.

The median progression-free survival (PFS) to worsening of grade/stage or death was 44.5 months. The median PFS to invasive/metastatic disease or death was 46.2 months. The 12-month PFS rate by either definition was 88.2%.

The median overall survival was not reached. The 12-month overall survival rate was 96.2%.

The rate of grade 3-4 treatment-related adverse events (TRAEs) was 14.4%, and 10.6% of patients discontinued therapy due to a TRAE. The most common TRAEs of any grade were pruritus (20.5%), hypothyroidism (13.6%), and fatigue (13.6%). There were no fatal TRAEs.

“These results are among the most robust data yet available for any novel systemic therapy in this patient population … and suggest that pembrolizumab monotherapy may be beneficial in this special patient population,” Dr Necchi concluded.

Disclosures: This research was supported by Merck Sharp & Dohme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Necchi A, Roumiguié M, Esen AA, et al. Pembrolizumab (pembro) monotherapy for patients (pts) with high-risk non–muscle-invasive bladder cancer (HR NMIBC) unresponsive to bacillus Calmette–Guérin (BCG): Results from cohort B of the phase 2 KEYNOTE-057 trial. ASCO GU 2023. February 16-18, 2023. Abstract LBA442.