AMBASSADOR
Trial question
What is the effect of adjuvant pembrolizumab in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
25.0% female
75.0% male
N = 702
702 patients (178 female, 524 male).
Inclusion criteria: patients with high-risk muscle-invasive urothelial carcinoma after radical surgery.
Key exclusion criteria: metastatic disease; active autoimmune disease; current pneumonitis or history of non-infectious pneumonitis that required corticosteroids within the previous 5 years; endocrine deficiencies; rheumatoid arthritis or other arthropathies; active hepatitis; postoperative/adjuvant systemic therapy.
Interventions
N=354 pembrolizumab (intravenous dose of 200 mg every 3 weeks for 1 year or until disease progression).
N=348 observation (observation every 3 weeks until disease progression).
Primary outcome
Median disease-free survival
29.6 months
14.2 months
29.6 months
22.2 months
14.8 months
7.4 months
0.0 months
Pembrolizumab
Observation
Significant
increase ▲
Significant increase in median disease-free survival (29.6 months vs. 14.2 months; HR 1.37, 95% CI 1.11 to 1.69).
Secondary outcomes
No significant difference in survival at 3 years (60.8% vs. 61.9%; HR 1.02, 95% CI 0.79 to 1.32).
Significant increase in median disease-free survival in patients with PD-L1-negative tumor expression (17.3 months vs. 9 months; HR 1.41, 95% CI 1.05 to 1.89).
No significant difference in median disease-free survival in patients with PD-L1-positive tumor expression (36.9 months vs. 21 months; HR 1.23, 95% CI 0.93 to 1.64).
Safety outcomes
Significant difference in grade ≥ 3 adverse events (50.6% vs. 31.6%).
Conclusion
In patients with high-risk muscle-invasive urothelial carcinoma after radical surgery, pembrolizumab was superior to observation with respect to median disease-free survival.
Reference
Andrea B Apolo, Karla V Ballman, Guru Sonpavde et al. Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2025 Jan 2;392(1):45-55.
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