In a discussion led by Prof Christof Vulsteke, a medical oncologist at the Integrated Cancer Center and Maria Middelares in Ghent, and Dr Michiel Strijbos, a medical oncologist at GZA Wilrijk, the potential impact of data from the EV-302/KEYNOTE-A39 and CheckMate 901 trials on bladder cancer management is examined.
The experts commence their conversation by underlining the significance of two groundbreaking studies. For many years, the standard approach for patients with locally advanced or metastatic urothelial carcinoma has been chemotherapy, followed by maintenance therapy if a positive response is achieved. However, two trials are poised to reshape this approach. The CheckMate 901 study assessed the combination of chemotherapy with immunotherapy, while the EV-302 trial investigated a chemotherapy-free regimen involving an antibody-drug conjugate and immunotherapy. Notably, the EV-302 trial reported an impressive overall survival of 31 months, in contrast to 16 months in the control arm—already surpassing the typical 13-month survival rate. The CheckMate 901 trial also demonstrated significantly improved overall survival compared to chemotherapy.
Dr Strijbos underscores the significance of these trials, particularly for patients with metastatic bladder cancer who are ineligible for chemotherapy. He emphasises the critical need for swift response in clinical practice, a requirement met by the EV-302 regimen, which boasts a response rate exceeding 70%. In contrast, conventional chemotherapy regimens typically yield only around 20% response rates. He highlights the importance of selecting the most suitable regimen upfront. Furthermore, the median duration of response has yet to be determined in the EV-302 trial, and the CheckMate 901 trial reported that 21% of patients achieved a complete response, with a duration of response exceeding 30 months. Given the often highly symptomatic nature of bladder cancer, the necessity for a rapid response cannot be overstated.
The experts discuss their approach to selecting the appropriate patients for the EV-pembrolizumab combination when it becomes available in clinical practice. Prof Vulsteke anticipates some concerns regarding the toxicity of the EV-302 trial. Notably, polyneuropathy can occur, particularly in the early cycles, though it is manageable. He expects a learning curve, especially as these drugs are used within a broader population of both patients and prescribers, each requiring tailored management. For instance, in patients with uncontrolled diabetes, glycemic control should be established before initiating treatment to prevent exacerbation of polyneuropathy. The duration of EV treatment may also warrant exploration, as it may not be necessary to wait for cumulative toxicity. Prof. Vulsteke notes that few contraindications for the EV-pembrolizumab combination are apparent, though the potential for alopecia induced by EV may be of concern to some patients.
Both experts concur that EV-pembrolizumab will become the new standard of care, impacting ongoing trials. Criticism may arise regarding the inclusion of the control arm as it may no longer represent the standard of care.
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