Clinical trialPhase 3Bladder cancer

Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma

N Engl J Med · 2025702 patients

Apolo AB, Ballman KV, Sonpavde G, Berg S, Kim WY, Parikh R, et al. N Engl J Med. 2025. 392:45-55

Study type: Clinical trial
Study name: AMBASSADOR
Phase: Phase 3
Design: Randomised trial (1:1) versus observation
Sample size: 702 patients
Source: N Engl J Med · 2025
Trial registration: NCT03244384

In plain words

In patients at high risk of the cancer coming back after removal of the bladder or urinary tract, one year of the immunotherapy drug pembrolizumab about doubled the time without the disease returning (median 29.6 versus 14.2 months), but severe side effects were also more common.

Key results

29.6 vs 14.2 months

Median disease-free survival

Hazard ratio 0.73 (0.59–0.90); P=0.003

50.6% vs 31.6%

Grade 3 or higher adverse events (regardless of attribution)

Drugs in this study:Pembrolizumab (Keytruda)

Dose and schedule cards

Adjuvant pembrolizumab (AMBASSADOR)

High-risk MIUC after radical surgery (≥ypT2 or N+ or positive margins after neoadjuvant therapy; or ≥pT3 or pN+ in patients ineligible for or declining cisplatin); this use is not included in the pembrolizumab FDA labelCycle length: Every 21 daysOn the page “Bladder cancer” · Muscle-invasive cancer (MIBC): after cystectomy (adjuvant)

Drug	Dose	Route	Schedule
Pembrolizumab	200 mg	IV over 30 minutes	Day 1 every 21 days

Cycle length: Every 21 days
Duration: 1 year (18 cycles) or until recurrence or toxicity

AMBASSADOR trial regimen.

On the page “Bladder cancer” · Muscle-invasive cancer (MIBC): after cystectomy (adjuvant)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Pembrolizumab

Pembrolizumab 200 mg IV over 30 minutes on day 1 every 21 days, for up to 1 year (18 cycles) or until recurrence or unacceptable toxicity (354 patients).

2Observation

Observation without treatment, with periodic imaging (348 patients).

Source of the regimen details: Full text of the paper (PMC11698643) and ClinicalTrials.gov NCT03244384

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

702 patients with muscle-invasive urothelial carcinoma (bladder, urethra or upper tract) or with positive lymph nodes, 4 to 16 weeks after radical surgery, in one of the high-risk groups: (1) after neoadjuvant chemotherapy with pathological stage ≥pT2 and/or N+‎ or positive margins; (2) unable to receive cisplatin (ECOG 2, creatinine clearance below 60 mL/min, grade 2 or higher hearing loss or neuropathy, or class III heart failure) or declining it, with ≥pT3 or pN+‎ or positive margins. Stratified by pathological stage, PD-L1 status and prior neoadjuvant chemotherapy.

Endpoints

Co-primary endpoints: disease-free survival and overall survival in the intention-to-treat population.

Safety and side effects

Grade 3 or higher adverse events (regardless of attribution) occurred in 50.6% of the pembrolizumab group and 31.6% of the observation group. Pembrolizumab was discontinued in 18.4% of patients because of adverse events and in 21.5% because of disease progression.

Clinical significance and place in guidelines

After CheckMate 274, AMBASSADOR is the second positive trial of adjuvant PD-1 inhibitor immunotherapy for disease-free survival; overall survival data are not presented in this report.

Limitations

The control group was observation (not placebo) and the trial was not blinded; overall survival results are not reported in the abstract.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.