The phase 3 AMBASSADOR trial's extended follow-up data, presented at the ESMO 2024 Congress, reinforces the disease-free survival (DFS) benefit of adjuvant pembrolizumab in patients with high-risk muscle-invasive urothelial carcinoma (MIUC). The study, involving approximately 700 patients, suggests pembrolizumab could become a valuable addition to the therapeutic options for this patient population.
The AMBASSADOR trial included patients with urothelial carcinoma of the upper tract, bladder, or urethra, predominantly urothelial carcinoma, who had undergone neoadjuvant chemotherapy or were cisplatin-ineligible and did not receive neoadjuvant cisplatin-based chemotherapy. The initial results, presented earlier in 2024, demonstrated a significant improvement in DFS with pembrolizumab compared to observation.
Sustained DFS Improvement
The updated data presented at ESMO 2024 confirms that the improvement in DFS is maintained with longer follow-up. While overall survival data is not yet mature, the DFS benefit observed with a hazard ratio of approximately 0.7 strengthens the case for pembrolizumab's use in the adjuvant setting.
According to Guru Sonpavde, MD, Medical Director of Genitourinary Oncology at AdventHealth Cancer Institute, these findings consolidate the role of pembrolizumab in the adjuvant setting. He noted that nivolumab is already approved for high-risk muscle-invasive disease, and the AMBASSADOR trial data could pave the way for pembrolizumab's approval as well, pending regulatory review.
PD-L1 and Tumor Location
An interesting observation from the trial is the lack of a clear trend for improved outcomes in patients with high PD-L1 expression. While PD-L1 was a secondary endpoint, this finding suggests that pembrolizumab's benefit may not be limited to PD-L1-positive tumors in this setting. Additionally, there was a trend towards improved outcomes in patients with primary bladder tumors compared to those with upper tract tumors, particularly in the renal pelvis. However, Dr. Sonpavde emphasized that these observations are hypothesis-generating and require further investigation.
Clinical Implications
The AMBASSADOR trial results suggest that adjuvant pembrolizumab could become a standard treatment option for patients with high-risk muscle-invasive urothelial carcinoma. The sustained DFS benefit, coupled with the existing approval of nivolumab in this setting, provides clinicians with additional tools to improve outcomes for patients facing this aggressive disease.
