Bladder Cancer Drug Trial Stopped After Survival Endpoint Achieved

Positive results in the KEYNOTE-045 clinical trial of Keytruda showed improved overall survival.

Merck recently announced that they have stopped the phase 3 trial of Keytruda (pembrolizumab) in patients with urothelial cancer because it met the primary endpoint of overall survival.

During an interim analysis of the KEYNOTE-045 trial, the Data Monitoring Committee recommended the trial be stopped early, Merck reported.

Included in the trial were 542 patients with metastatic or locally advanced or unresectable urothelial cancer that recurred or progressed on platinum-based chemotherapy. The co-primary endpoints were overall survival and progression-free survival, and the secondary endpoints were overall response rate, duration of response, and safety.

Patients were randomized to receive Keytruda or a choice of chemotherapies (paclitaxel, docetaxel, or vinfluine). Researchers found that Keytruda was superior to any of the chemotherapies investigated, and demonstrated better overall survival as well.

They also noted that the safety profile was consistent with what was previously discovered. Several immune-mediated conditions can occur, such as pneumonitis, colitis, hepatitis, and nephritis. Other adverse effects include hypophysitis, hyperthyroidism, and type 1 diabetes.

Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, which activates T cells. It is currently indicated for use in patients with melanoma, lung cancer, and head and neck cancer.

Other recent findings suggest that Keytruda may be a promising first-line treatment for advanced lung cancer with high PD-L1 expression. Keytruda is being explored in over 30 different types of cancer in over 300 trials.

Merck reports that they have the largest immuno-oncology clinical development program for bladder cancer, including 27 trials that investigate Keytruda as a monotherapy and combination therapy.

“The results of KEYNOTE-045 represent a major breakthrough and will be welcome news for patients dealing with previously treated advanced urothelial cancer,” said Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories. “We look forward to sharing the findings from this study with the medical community and with regulatory authorities around the world.”