New Hope for Cisplatin-Ineligible Bladder Cancer Patients: Enfortumab Vedotin & Pembrolizumab Combination Shows Promise
Groundbreaking results unveiled at ESMO 2025 demonstrate a significant advancement in the treatment of muscle-invasive bladder cancer (MIBC) for patients unable to receive cisplatin chemotherapy. A phase 3 trial, KEYNOTE-905, reveals that a combination of enfortumab vedotin (EV) and pembrolizumab (pembro) dramatically improves outcomes, offering a potential new standard of care.
Understanding Muscle-Invasive Bladder Cancer and Cisplatin Ineligibility
Muscle-invasive bladder cancer (MIBC) is an aggressive form of the disease where cancer cells penetrate the bladder muscle. Treatment typically involves a combination of surgery, chemotherapy, and potentially radiation. Cisplatin-based chemotherapy has long been a cornerstone of treatment, but a substantial portion of patients – often due to pre-existing kidney problems, hearing loss, or other health conditions – are ineligible to receive it. This leaves a critical unmet need for effective alternative therapies.
KEYNOTE-905: A Landmark Study
The KEYNOTE-905 trial, a randomized, phase 3 study, investigated the efficacy of perioperative enfortumab vedotin plus pembrolizumab in patients with MIBC who were cisplatin-ineligible. The trial involved patients receiving EV and pembro before and after surgical removal of the bladder (cystectomy). Initial findings, presented at the European Society for Medical Oncology (ESMO) 2025 congress, indicate a remarkable 60% reduction in the risk of disease progression or death compared to standard neoadjuvant chemotherapy. UroToday provides further details on the study design.
Padcev and Keytruda Combination Also Shows Promise
Alongside the KEYNOTE-905 results, positive data emerged from the phase 3 ev-303 trial evaluating Padcev (enfortumab vedotin) in combination with Keytruda (pembrolizumab). Pfizer and Astellas announced these findings, indicating a synergistic effect when the two agents are used together. This combination is being explored both before and after surgery, potentially maximizing treatment benefits.
What impact will these findings have on the future of bladder cancer treatment? And how will these new regimens be integrated into clinical practice for cisplatin-ineligible patients?
The combination of enfortumab vedotin and pembrolizumab represents a significant step forward, offering a much-needed option for patients with MIBC who previously faced limited treatment choices. The data presented at ESMO 2025 are expected to influence clinical guidelines and improve outcomes for this challenging patient population. The American Journal of Managed Care highlights the 60% risk reduction in disease progression or death.
Frequently Asked Questions About Enfortumab Vedotin and Pembrolizumab for Bladder Cancer
What is enfortumab vedotin and how does it work in bladder cancer?
Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a protein often found in high levels on bladder cancer cells. It delivers a chemotherapy drug directly to the cancer cells, minimizing damage to healthy tissues.
Who is considered cisplatin-ineligible for bladder cancer treatment?
Patients with pre-existing kidney problems, hearing loss, neuropathy, or other medical conditions that would make cisplatin unsafe are considered cisplatin-ineligible.
What are the potential side effects of combining enfortumab vedotin and pembrolizumab?
Common side effects may include fatigue, skin reactions, peripheral neuropathy, and immune-related adverse events. Patients should discuss potential side effects with their healthcare team.
How does the KEYNOTE-905 trial change the treatment landscape for MIBC?
The KEYNOTE-905 trial provides strong evidence supporting the use of enfortumab vedotin and pembrolizumab as a viable and effective alternative to cisplatin-based chemotherapy for cisplatin-ineligible patients with MIBC.
Is the Padcev and Keytruda combination available now?
The Padcev and Keytruda combination is still under review by regulatory agencies, but the positive results from the ev-303 trial suggest it may become a treatment option in the near future. FirstWord Pharma reports on the latest developments.
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