For the first time in decades, significant advancements in treating advanced bladder cancer have emerged, highlighted by the combination of enfortumab vedotin (Padcev) and pembrolizumab (Keytruda) demonstrating a doubling of survival rates compared to standard chemotherapy. These findings, stemming from the EV-302 and CheckMate-901 trials, mark a pivotal moment in bladder cancer treatment, offering new hope for patients with advanced disease.
Landmark Trial Results
The EV-302 trial, a study involving nearly 900 patients, compared the efficacy of enfortumab plus pembrolizumab against traditional chemotherapy regimens. The results, presented at the European Society for Medical Oncology (ESMO) annual meeting, revealed a median overall survival of 31 months in the combination therapy arm, nearly double the 16 months observed in the chemotherapy arm. This improvement marks the first instance of a therapy surpassing chemotherapy in extending survival as an initial treatment for advanced bladder cancer.
Thomas Powles, M.D., lead investigator of EV-302 from Barts Cancer Institute, Queen Mary University of London, emphasized the significance of this achievement, noting that tumor shrinkage or growth cessation occurred in approximately 67% of participants treated with the combination, compared to 44% in the chemotherapy group. Moreover, complete responses, where the cancer disappeared entirely, were observed in almost 30% of patients receiving enfortumab plus pembrolizumab, a rate significantly higher than the 12% in the chemotherapy group.
CheckMate-901 Trial
In parallel, the CheckMate-901 trial assessed the impact of adding nivolumab (Opdivo) to standard chemotherapy. This study, involving approximately 600 patients, found that the addition of nivolumab extended the median overall survival to 22 months, compared to 19 months with chemotherapy alone. Furthermore, the median length of complete remission was about 3 years, triple the length of remission in those who received chemotherapy alone.
Implications for Clinical Practice
Andrea Apolo, M.D., of NCI’s Genitourinary Malignancies Branch, has hailed enfortumab plus pembrolizumab as the new standard of care for initial treatment of advanced bladder cancer. The combination therapy not only demonstrated the highest percentage of patients experiencing tumor shrinkage or growth cessation but also offered patients the best chance at prolonged survival.
Considerations and Future Directions
While these advancements represent a significant leap forward, they also raise important questions about treatment sequencing, the potential role of additional immunotherapy, and the underlying mechanisms driving the efficacy of enfortumab and pembrolizumab. Cost considerations and ensuring equitable access to these expensive treatments are also critical aspects that need to be addressed.
Further research is warranted to optimize treatment strategies and address potential resistance mechanisms. Understanding the synergistic effects of enfortumab and pembrolizumab could pave the way for new therapeutic approaches and preventive measures.
