Researchers observed a 60% reduction in the risk of relapse and a 50% reduction in the risk of death thanks to this combination administered before and after surgery. A world first that could well transform the treatment of bladder cancer.
Invasive bladder cancer, a particularly aggressive form
Every year, nearly 12,000 French people learn that they have bladder cancer. For 20 to 30% of them, the tumor in question is invasive, it infiltrates the muscle of the bladder. Invasive tumors have a poor prognosis: only half of the patients are still alive five years after surgical removal of the bladder, the standard treatment for this form of cancer. But almost half of them cannot receive chemotherapy with cisplatin, which is too toxic for their kidneys. or their weakened body (given before to reduce the size of the tumor or after to destroy the remaining cancer cells). In the absence of an effective alternative, recurrences were frequent and the prospects for survival were limited.
It is this brutal observation that the KEYNOTE-905 / EV-303 study sought to respond to, an international phase III trial conducted in 344 patients not eligible for cisplatin. Its objective: to test the effectiveness of two treatments already used at other stages of the disease, pembrolizumab (Keytruda®), an immunotherapeutic antibody, and enfortumab vedotin (Padcev®), a drug targeting tumor cells.
A dramatic reduction in the risk of death
The results presented at the ESMO 2025 congress sent shockwaves. In patients treated with Keytruda® and Padcev®, the risk of relapse-free survival events decreased by 60% and the risk of death by 50% compared to surgery alone. The pathological complete response rate, that is to say the absence of detectable cancer after the operation, reached 57.1%, compared to only 8.6% in the control group.
Dr. Jonathan Rosenberg of Memorial Sloan Kettering Cancer Center summarizes the significance of these findings: “These results demonstrate that the perioperative combination of enfortumab vedotin and pembrolizumab significantly improves outcomes for patients with muscle-invasive bladder cancer who cannot receive cisplatin.”.
For Christof Vulsteke, oncologist at AZ Maria Middelares Hospital in Belgium, the message is clear: “This combination could represent a new standard of treatment for this difficult-to-treat population.“.
A perspective that is changing the way the medical community now views the management of this aggressive cancer.
Side effects under surveillance, and hope confirmed by the FDA
While the benefits are major, researchers remain cautious about the side effects observed. Nearly 71% of treated patients experienced high-grade adverse reactions, including severe skin reactions. Despite this, experts emphasize that the safety profile remains generally consistent with what had already been observed in other indications.
For patients not eligible for cisplatin, often excluded from therapeutic advances, this study marks a turning point. The Food and Drug Administration (FDA), the American drug agency, has also granted this association priority review, a crucial step which could lead to rapid authorization in this indication.
Other trials are already underway to evaluate these treatments in earlier stages or in combination with other immunotherapies.