preheader BJMO

Pembrolizumab monotherapy for patients with high-risk non-muscle-invasive bladder cancer unresponsive to bacillus Calmette-Guérin

At ASCO GU 2023, Prof. Necchi presented the results from cohort B of the phase II Keynote-052 trial, investigating pembrolizumab monotherapy for patients with high-risk non-muscle-invasive bladder cancer (HR NMIBC) unresponsive to bacillus Calmette-Guérin (BCG). Pembrolizumab showed antitumour activity in terms of disease-free survival rate in patients with BCG unresponsive papillary HR NMIBC and has a manageable adverse event profile.

The standard of care for patients with high-risk non-muscle-invasive bladder cancer (HR NMIBC) is transurethral resection of the bladder tumour (TURB), followed by therapy with intravesical bacillus Calmette-Guérin (BCG). Unfortunately however, prognosis is poor for patients whose disease does not respond to BCG or relapses within 12 months and these patients are still directed to radical cystectomy (RC). The multicohort phase II Keynote-057 trial evaluated the efficacy and safety of pembrolizumab monotherapy in patients with BCG-unresponsive HR NMIBC who were ineligible for or declined RC. Results from cohort A (carcinoma in situ [CIS] with or without papillary tumours) showed a clinical complete response (CR) rate at three months of 40.6%, with a median duration of response of 16.2 months, resulting in the US FDA approval of pembrolizumab for these patients. At ASCO GU 2023, results from cohort B (papillary tumours only, without CIS) were presented.

Study design

Adult patients with BCG-unresponsive HR NMIBC with papillary tumours only (high-grade Ta or any-grade T1) at baseline and ECOG PS 0-2. Patients received pembro 200 mg every 3 weeks (Q3W) for ≤35 cycles (~2 year). Cancer was assessed at 12 weeks and Q12W thereafter if no recurrent HR NMIBC or progression was observed. A CT urography was done Q24W. Primary endpoints for cohort B were 12-month disease-free survival (DFS) rate of HR NMIBC as assessed by central pathology/radiology review and safety, assuming a 12-month DFS of >20% for HR NMIBC. Secondary efficacy endpoints were 12-month DFS rate of any disease; progression-free survival (PFS) to worsening of grade, stage, or death; PFS to muscle invasion, metastasis, or death; and overall survival (OS).


Overall, 132 patients received pembrolizumab for a median of 9.5 cycles (range, 1.0-35.0). Median age was 72 years, 43% had T1 stage, all patients (100%) had urothelial histology and 79% were male. Patients received a median of 10 prior BCG instillations. Median follow-up was 45.4 months. Median DFS for HR NMIBC was 7.7 months and the 12-month DFS rate was 43.5%. The curve is plateauing after month 24, resulting in the equal estimated 24- and 36-month DFS rate of 34.9%. Median DFS for any disease was 6.0 months and 12-, 24- and 36-month DFS rates were 41.7%, 33.0% and 33.0%, respectively. Results were consistent, regardless of prior baseline patient and disease characteristics. The median PFS to worsening of grade or stage or death was 44.5 months and the median PFS to muscle-invasive or metastatic disease or death was 46.2 months. Median OS was not reached and the 12-month OS rate was 96.2%.

Median treatment duration was 6.3 months. Treatment-related adverse events (TRAEs) occurred in 73.5% of patients and 14.4% had a grade 3-4 TRAE. The most common grade 3-4 TRAEs were pruritus (20.5%), hypothyroidism (13.6%), diarrhoea (7.6%) and colitis (2.3%). Immune-mediated AEs and infusion reactions of grade 3-4 occurred in 30.3% of patients. Fourteen patients (10.6%) discontinued treatment due to a TRAE. No deaths from TRAEs occurred. Finally, most patients had a stable or improved quality of life.


Pembrolizumab showed antitumour activity in patients with BCG-unresponsive papillary HR NMIBC after approximately 45 months of follow-up. Pembrolizumab had a manageable safety profile consistent with that observed in cohort A, with no new safety signals, no treatment-related deaths and a stable/consistent quality of life during treatment. These results are among the most robust data in terms of sample size and follow-up duration for a novel systemic therapy used to treat papillary HR NMIBC. Results suggest patients with papillary HR NMIBC unresponsive to BCG who declined or were ineligible for RC may benefit from pembrolizumab monotherapy.


Necchi A, 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. Presented at ASCO GU 2023; Abstract LBA442.

Speaker Andrea Necchi

Andrea Necchi

Andrea Necchi, MD, PhD, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy


See: Keyslides

Back to Top