Pembrolizumab Improves DFS in Muscle-Invasive Urothelial Carcinoma


Meeting a primary end point, KEYNOTE-123 study shows promise for pembrolizumab as an adjuvant muscle-invasive bladder cancer treatment.

Human urinary system: ©magicmine -

Human urinary system: ©magicmine -

The phase 3 AMBASSADOR trial (NCT03244384) met one of its 2 primary end points of disease-free survival (DFS). The trial is evaluating pembrolizumab (Keytruda) for adjuvant treatment of localized muscle-invasive urothelial carcinoma (MIUC) and locally advanced urothelial carcinoma in patients who have already had surgery.

The trial, also referred to as KEYNOTE-123, will continue to evaluate the other primary end point of overall survival (OS). Pembrolizumab’s safety profile was consistent with what was observed in previous studies, and investigators did not identify any new safety signals.

“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,” said Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, said in a press 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.”1

An estimated 739 patients are enrolled in KEYNOTE-123. The secondary end points are OS and DFS in PD-L1 positive and negative patients. In the study, patients receive intravenous pembrolizumab over 30 minutes on day 1, and treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or toxicity. Patients are monitored via CT scan, CT urography, and/or MRI throughout the trial.

To be eligible to participate in the study, patients cannot have active or historical autoimmune disease or other endocrine disorders. The estimated study completion date is June 2025.2

Pembrolizumab is FDA-approved as a primary and adjuvant treatment for a variety of cancers, including Hodgkin lymphoma, head and neck cancer, and melanoma. to treat a variety of cancers. The FDA previously approved pembrolizumab to treat high-risk, non-muscle invasive bladder cancer.3

Several additional studies are assessing pembrolizumab in patients with bladder cancer, both muscle-invasive and non-muscle invasive. KEYNOTE-866 (NCT03924856) in phase 3 and is evaluating perioperative pembrolizumab plus neoadjuvant chemotherapy for cisplatin-eligible muscle-invasive bladder cancer. An estimated 907 patients are enrolled, and the study also has a June 2025 estimated completion date.4 One phase 2 study (NCT05072600) is assessing pembrolizumab as a maintenance monotherapy in MIUC, and another phase 2 trial (NCT02736266) is looking at pembrolizumab as a neoadjuvant therapy for MIUC.5,6

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 4, 2023. Accessed October 5, 2023.
2. Testing MK-3475 (Pembrolizumab) after surgery for localized muscle-invasive bladder cancer and locally advanced urothelial cancer (AMBASSADOR). Updated September 26, 2023. Accessed October 5, 2023.
3. Is Keytruda right for you? Keytruda. Accessed October 5, 2023.
4. Perioperative pembrolizumab (MK-3475) plus neoadjuvant chemotherapy versus perioperative placebo plus neoadjuvant chemotherapy for cisplatin-eligible muscle-invasive bladder cancer (MIBC) (MK-3475/KEYNOTE-865) (KEYNOTE-866). Updated August 30, 2023. Accessed October 5, 2023.
5. Pembrolizumab monotherapy following tri-modality treatment for selected patients with muscle-invasive bladder cancer. Updated January 10, 2022. Accessed October 5, 2023.
6. Neoadjuvant pembrolizumab for muscle-invasive urothelial carcinoma (PURE-01). Updated July 18, 2023. Accessed October 5, 2023.
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