A 60% Reduction in Risk: How Enfortumab Vedotin & Pembrolizumab Are Redefining Bladder Cancer Treatment
For half of all patients diagnosed with muscle-invasive bladder cancer (MIBC), cisplatin-based chemotherapy isn’t an option – either due to pre-existing conditions or patient choice. Until recently, this meant significantly poorer outcomes. But new data reveals a paradigm shift: a combination of enfortumab vedotin (EV) plus pembrolizumab slashed the risk of disease progression or death by a remarkable 60% in this challenging patient population. This breakthrough, demonstrated in the KEYNOTE-905 trial, isn’t just incremental; it’s the first to show an overall survival benefit for cisplatin-ineligible MIBC patients, signaling a new era in treatment.
The KEYNOTE-905 Trial: A Game Changer for Cisplatin-Ineligible Patients
Presented at the 50th European Society for Medical Oncology Congress, the KEYNOTE-905 trial focused on a population often overlooked in cancer research – older patients (median age 73) with compromised kidney function or other health issues that preclude cisplatin treatment. Dr. Christof Vulsteke, principal investigator of the study, emphasized the stark contrast in outcomes. While just 39% of patients in the surgery-alone control arm were event-free at two years, a striking 75% in the EV-pembrolizumab arm achieved the same milestone. This translated to a significant improvement in overall survival, with 80% of patients in the treatment arm still alive at two years compared to 63% in the control group.
Unprecedented Pathological Complete Response Rates
Beyond event-free and overall survival, the trial delivered another compelling result: a pathological complete response (pCR) rate of 57.1%. This means that, after surgery, over half of the patients treated with EV plus pembrolizumab showed no remaining cancer cells in their bladders – the highest pCR ever reported in this setting. This level of response offers the potential for long-term remission and, crucially, may reduce the need for radical cystectomy, a major surgery with significant comorbidities.
Consistency Across Subgroups: A Broadly Effective Treatment
One of the most encouraging aspects of the KEYNOTE-905 trial was the consistent benefit observed across all patient subgroups. Whether considering PD-L1 expression levels, histologic variants of bladder cancer, or clinical stage, EV plus pembrolizumab demonstrated a clear advantage. This suggests the treatment’s efficacy isn’t limited to a specific subset of patients, broadening its potential impact.
Managing Treatment-Related Toxicities
As with any powerful cancer regimen, EV plus pembrolizumab isn’t without side effects. The most common toxicities, consistent with observations in metastatic settings, include skin reactions (affecting over 60% of patients, with severe cases in around 10%) and polyneuropathy (reported in 38%). However, Dr. Vulsteke stressed that these side effects are manageable with experience and proactive monitoring. Close communication between patient and physician is vital, with prompt intervention – including drug holidays – for grade 3 toxicities.
Surgery and Sequencing: A Seamless Integration
A key concern with perioperative regimens is the potential for treatment-related delays in surgery. Fortunately, the KEYNOTE-905 trial showed that EV plus pembrolizumab did not worsen surgical complications or delay the timing of surgery. This seamless integration is crucial for maximizing treatment effectiveness and minimizing patient burden.
Looking Ahead: The Future of MIBC Treatment
While the KEYNOTE-905 trial focused on cisplatin-ineligible patients, the results are prompting a re-evaluation of the entire MIBC treatment landscape. The upcoming EV-304 trial (NCT04700124) will investigate the efficacy of EV plus pembrolizumab in cisplatin-eligible patients, potentially expanding the treatment’s reach even further. Dr. Vulsteke envisions a future where treatments like EV plus pembrolizumab pave the way for bladder-sparing approaches, potentially eliminating the need for radical cystectomy altogether. This represents a significant step towards a more personalized and less invasive approach to bladder cancer care.
The promise of avoiding radical cystectomy – a procedure with substantial impact on quality of life – is particularly exciting. As research continues and our understanding of bladder cancer evolves, the combination of enfortumab vedotin and pembrolizumab is poised to become a cornerstone of treatment, offering hope and improved outcomes for a wider range of patients.
What are your thoughts on the potential for bladder-sparing therapies in MIBC? Share your perspective in the comments below!
