Treatment with adjuvant pembrolizumab (Keytruda) reduced the risk of disease recurrence or death versus observation in patients with localized muscle-invasive urothelial carcinoma (MIUC) and locally advanced urothelial carcinoma, according to findings from the phase 3 AMBASSADOR trial (NCT03244384).1
Merck (MSD), the manufacturer of pembrolizumab, reported in a news release that an independent Data Monitoring Committee determined at a pre-specified interim analysis that treatment with the PD-1 inhibitor after surgery significantly improved disease-free survival (DFS) in this patient population. DFS is a co-primary end point of the trial along with overall survival (OS). The study is continuing in order to evaluate OS.
There were no new safety signals observed with pembrolizumab compared with previously published research with the immunotherapy. Merck plans to share the specific data from the trial at an upcoming meeting and communicate with regulatory authorities about the findings.
“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,” Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, stated in the news release. “These positive results highlight the potential of Keytruda to prevent recurrence after surgery for patients with localized muscle-invasive or locally advanced urothelial carcinoma.”
Overall, the open-label phase 3 AMBASSADOR trial enrolled 702 patients with MIUC and locally advanced urothelial carcinoma. Patients were randomized to observation or post-surgery pembrolizumab at 200 mg IV every 3 weeks for a maximum of 18 cycles. The trial was sponsored by the National Cancer Institute and was open at more than 900 clinical sites.
Patients were monitored throughout the trial with CT, CT urography, and/or MRI. The study design allowed for patients to receive a cystoscopy and blood sample collection at the time of screening and on the study.
Pembrolizumab currently has several FDA approvals for the treatment of patients with urothelial carcinoma:
Regarding the adjuvant treatment of genitourinary cancers, pembrolizumab is approved by the FDA as an adjuvant therapy for patients with renal cell carcinoma who are at intermediate-high or high risk of having disease recurrence after undergoing nephrectomy, or after receiving nephrectomy and resection of metastatic lesions.2
1. KEYTRUDA significantly improved DFS as adjuvant therapy versus observation for patients with localized MIUC and locally advanced urothelial carcinoma. Published online 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. Highlights of prescribing information: KEYTRUDA® (pembrolizumab) injection, for intravenous use Initial U.S. Approval: 2014. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf