Adjuvant Pembrolizumab Improves DFS in Localized Urothelial Cancer

Pembrolizumab (Keytruda) as adjuvant therapy led to a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared with observation in patients with localized muscle invasive urothelial cancer (MIUC) and locally advanced urothelial cancer, meeting one of the dual primary end points of the phase 3 AMBASSADOR/KEYNOTE-123 trial (NCT03244384; A031501).¹

Findings, which were reported from a prespecified interim analysis conducted by an independent data monitoring committee, also demonstrated no new safety signals with the PD-1 inhibitor. The other dual primary end point of overall survival (OS) will continue to be evaluated.

Data from the trial will be presented at an upcoming medical meeting and shared with regulatory agencies. 

“Up to half of patients with bladder cancer who undergo surgery will experience recurrence within a year, underscoring the need for new treatment options in the adjuvant setting,” Dr Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, stated in a news release. “These positive results highlight the potential of [pembrolizumab] to prevent recurrence after surgery for patients with localized muscle-invasive or locally advanced urothelial carcinoma.”

AMBASSADOR is the second trial to demonstrate positive DFS outcomes with a checkpoint inhibitor in this population. Previously, nivolumab (Opdivo) led to improvements in DFS and OS vs placebo in patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection. Findings, which were reported from the phase 3 CheckMate-274 trial (NCT02632409), served as the basis for the agent’s FDA approval in this population in August 2021.²

To be eligible for enrollment in the randomized, open-label, phase 3 trial, patients had to have histologically confirmed MIUC of the bladder, urethra, or upper tract, or lymph node–positive disease; no evidence of residual cancer or metastasis after surgery; and available paraffin tissue samples. Variant histology was allowed if urothelial carcinoma represented the majority of patients.³

A total of 702 patients were randomly assigned to receive 200 mg of intravenous pembrolizumab every 3 weeks for up to 18 cycles or observation.¹

In addition to the dual primary end points of OS and DFS, secondary end points include OS and DFS in patients with PD-L1–positive and –negative disease, as well as the safety and tolerability of the agent.

References

1. Merck’s KEYTRUDA (pembrolizumab) met primary endpoint of disease-free survival (DFS) in certain patients with muscle-invasive urothelial carcinoma (MIUC) after surgery. News release. Merck. October 5, 2023. Accessed October 5, 2023. https://www.merck.com/news/mercks-keytruda-pembrolizumab-met-primary-endpoint-of-disease-free-survival-dfs-in-certain-patients-with-muscle-invasive-urothelial-carcinoma-miuc-after-surgery/
2. US Food and Drug Administration approves Opdivo (nivolumab) for the adjuvant treatment of patients with high-risk urothelial carcinoma. News release. Bristol Myers Squibb. August 20, 2021. Accessed October 5, 2023. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab-for-the-Adjuvant-Treatment-of-Patients-with-High-Risk-Urothelial-Carcinoma/default.aspx
3. Testing MK-3475 (pembrolizumab) after surgery for localized muscle-invasive bladder cancer and locally advanced urothelial cancer (AMBASSADOR). ClinicalTrials.gov. Updated September 26, 2023. Accessed October 5, 2023. https://clinicaltrials.gov/study/NCT03244384