(UroToday.com) The 2024 ESMO annual meeting included a session on urothelial carcinoma, featuring a presentation by Dr. Andrea Apolo, discussing extended follow-up for disease free survival and an assessment of metastatic disease recurrence pattern from the AMBASSADOR study of adjuvant pembrolizumab in muscle-invasive urothelial carcinoma versus observation. Muscle invasive urothelial carcinoma is an aggressive disease with a noted high relapse rate. Previously, the AMBASSADOR study demonstrated a significant improvement in disease free survival (with 22 month follow-up) for adjuvant pembrolizumab versus observation in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery. At ESMO 2024, Dr. Apolo and colleagues reported extended disease free survival (with 45 month follow-up) analyses, sites of metastatic recurrence, and lymph node status outcomes.
This is an open label, randomized, phase 3 trial that enrolled patients with muscle-invasive urothelial carcinoma of the bladder, upper tract, or urethra. Patients were randomized 1:1 to receive pembrolizumab 200 mg every 3 weeks for 1 year or observation. The dual primary endpoints were disease free survival and overall survival. Final overall survival analysis requires additional events:
Overall, 702 patients were randomized, and the median disease free survival follow-up was 44.8 months (range: 0.03-70.1). A summary of the baseline characteristics is provided below:
With additional follow-up, the primary endpoint of disease free survival in the intention to treat population still showed a significant benefit for pembrolizumab (median 29.6 months) versus observation (median 14.2 months; HR 0.73, 95% CI 0.59-0.90):
The disease free survival benefit for pembrolizumab was consistent across most subgroups, in particular regardless of PD-L1 status:
When assessing disease free survival by lymph node stage in all patients, it is noted that with increasing lymph node stage, patients generally had worse outcomes. However, all patients did better with pembrolizumab versus observation:
Similar findings were noted for lower urinary tract by lymph node stage:
However, data is inconclusive secondary to a small sample size for upper tract urothelial carcinoma by lymph node stage. Common sites of metastasis included lymph node, pelvic mass, lung, bone, and liver:
Dr. Apolo concluded her presentation by discussing extended follow-up for disease free survival and an assessment of metastatic disease recurrence pattern from the AMBASSADOR study with the following take-home points:
- Adjuvant pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in disease free survival versus observation for patients with high risk muscle invasive urothelial carcinoma after radical surgery with extended follow-up of 45 months
- Subgroup analysis showed a disease free survival benefit with pembrolizumab versus observation regardless of PD-L1 expression and lymph node status
- Metastatic recurrences were more common in patients on observation versus pembrolizumab, with common sites being the lymph nodes, lung, bone, and liver
- Based on the doubling of the median disease free survival and manageable toxicity, this trial supports the use of adjuvant pembrolizumab as a therapeutic option in patients with high risk muscle invasive urothelial carcinoma
Presented by: Andrea B. Apolo, MD, National Cancer Institute, Bethesda, MD
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 European Society of Medical Oncology (ESMO) Annual Meeting, Barcelona, Spain, Fri, Sept 13 – Tues, Sept 17, 2024.
Related Content:
AMBASSADOR Trial: Extended Follow-up on Adjuvant Pembrolizumab in Bladder Cancer - Andrea Apolo
Apolo, A.B. et al. (2024) ‘Adjuvant pembrolizumab versus observation in muscle-invasive urothelial carcinoma’, New England Journal of Medicine [Preprint]. doi:10.1056/nejmoa2401726.