Systemic Therapy for Cisplatin-Ineligible Patients With Bladder Cancer


Expert perspectives on first-line treatment options available to patients with advanced bladder cancer who are ineligible for cisplatin-based chemotherapy.


Petros Grivas, MD, PhD: Nerina, we deal with these patients in the clinic every day. For cisplatin-ineligible patients, based on the criteria you very nicely outlined, we have 3 options. We have carboplatin and gemcitabine, and we can talk about maintenance available in a second. As of April, we have pembrolizumab plus enfortumab as an option based on the accelerated approval by the FDA for cisplatin-ineligible patients. And of course, we have clinical trials, which are my 2 favorite words. Always think about clinical trials. [Do you have] any comments about that clinical decision-making? Obviously, the shortcuts may be relevant here. If you don’t have a drug, you go to the other combo. But I have given pembrolizumab–EV [enfortumab vedotin] in clinical practice to a few patients of trial. Any comments or considerations on toxicity profile, medical comorbidities, or neuropathy that come to mind when we try to make this decision?

Nerina T. McDonald, PA-C: As you were saying, it’s a case-by-case basis [depending on] how the patient is coming into therapy and what their goals of care and priorities are. If a patient already has some degree of underlying neuropathy or uncontrolled diabetes, then maybe enfortumab isn’t a great option for them. But in most contexts, the pembrolizumab–EV [enfortumab vedotin] route is a great way to go.

Petros Grivas, MD, PhD: I agree. Especially for patients with explosive disease and visceral metastases, you’re trying to achieve a response. The response rate with pembrolizumab–EV [enfortumab vedotin] is about 65% or so. Carboplatin-gemcitabine is about 40%, 42%. Not to compare them directly, but if you want to go for a response, pembrolizumab–EV [enfortumab vedotin] is a great option for cisplatin-ineligible patients. Nerina, we have this trial open, the EV-302, that compares platinum gemcitabine chemotherapy vs pembrolizumab–EV [enfortumab vedotin]. We’re excited to see the data from that trial and how patients are holding.

Nerina T. McDonald, PA-C: Right.

Petros Grivas, MD, PhD: It’s very interesting. Lisa, [do you have] any comments about that decision-making, pembrolizumab–EV [enfortumab vedotin] vs carboplatin-gemcitabine? It’s an ongoing debate at conferences.

Lisa Adams, PA-C: Definitely. My feeling about which patients may be interested in up-front carboplatin-gemcitabine or cisplatin-gemcitabine is that the fixed time frame of cytotoxic chemotherapy is 4 to 6 cycles. With pembrolizumab–EV [enfortumab vedotin], they might have cumulative toxicities from being on it until progression or toxicity. Thinking about that, maybe the limited time point of platinum-based chemotherapy is more attractive for some patients.

Petros Grivas, MD, PhD: Thank you, Lisa. It’s an interesting discussion with the patients as well as multifactorial.

Transcript edited for clarity.

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