Guru Sonpavde, MD, on phase 3 AMBASSADOR trial data in urothelial carcinoma

In this video, Guru P. Sonpavde, MD, highlights the background and key findings from the trial, “Alliance A031501: AMBASSADOR study of adjuvant pembrolizumab (Pembro) in muscle-invasive urothelial carcinoma (MIUC) vs observation (Obs): Extended follow-up disease-free survival (DFS) results and metastatic (met) disease recurrence distribution,” which was presented at the 2024 ESMO Congress in Barcelona, Spain. Sonpavde in the Medical Director of Genitourinary Oncology, Assistant Director of the Clinical Research Unit, and Christopher K. Glanz Chair for Bladder Cancer Research at AdventHealth Cancer Institute in Orlando, Florida.

Video Transcript:

AMBASSADOR is a phase 3 trial that evaluated adjuvant pembrolizumab in patients with high-risk muscle-invasive urothelial carcinoma. These are patients with either upper tract or bladder or urethral carcinoma, with predominantly urothelial carcinoma. These were patients who had neoadjuvant chemo, or they may have been cisplatin-ineligible and not had neoadjuvant cisplatin-based chemo. The trial has been already reported as positive at the GU ASCO symposium earlier this year in 2024, and essentially, there was an improvement in disease free survival. There's an update at ESMO 2024 here, which shows that the improvement in DFS is maintained after a longer follow-up. Now survival has not been met, but survival is a secondary end point, and the DFS improvement was with a hazard ratio of approximately 0.7, which is what was reported at the GU ASCO Symposium.

I think that these data in this approximately 700 patient trial consolidates and makes a strong case for the role of pembrolizumab in the adjuvant setting. As we know, nivolumab is already approved in this adjuvant setting, high-risk muscle invasive disease in all-comers in the US and in P-L1 high patients only in Europe. So, with this AMBASSADOR trial, we expect pembrolizumab might also be available at some point in the future in the clinic, so we need to wait for regulatory agencies to look at the data and tell us.

Now, one of the interesting findings in this trial, which has been reported before, was there was not a trend for improved outcomes in the PD-L1 high population. So, that did not fall out. That was not a primary end point, to look at PD-L1 alone; it was a secondary end point. There does seem to be a trend for improved outcomes in the bladder primary as opposed to upper tract, especially renal pelvis. That was seen actually across both those [readouts]. But those are hypothesis generating. So, at the end of the day, adjuvant pembrolizumab, we think, could be added to the therapeutic armamentarium for the adjuvant therapy of patients with high-risk muscle-invasive urothelial carcinoma.

This transcription has been edited for clarity.