Dosing, Cycle Considerations With EV/Pembrolizumab Combination

A roundtable discussion, moderated by Thomas Powles, MBBS, MRCP, MD, covered the latest updates in bladder cancer treatment and research, including recent data from ESMO 2023. Dr. Powles was joined by Shilpa Gupta, MD; Sia Daneshmand, MD; and Petros Grivas, MD.

In the next segment of the roundtable series, the panel discussed optimal treatment cycles for enfortumab vedotin/pembrolizumab as related to potential treatment-related toxicities.

Watch the next segment in this series.

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Dr. Powles: Do you think that in terms of the number of cycles, the average… Shilpa said that we got to 12, which I think is true for both drugs, but are you pushing the enfortumab vedotin (EV) through? Or are you getting to 6 or 8 or 10 cycles and beginning to say to patients, “You know what? We might miss day 8; we might do 3 weekly cycles. We’ll come down a bit on the dose.” What’s your take on that?

Dr. Grivas: Tom, traditionally over the last few years since enfortumab was approved by the FDA, I take the approach of starting in most patients, at least not that frail, but most patients with full dose. But I literally look for reasons to dose reduce. After the first 1 or 2 cycles usually people have some degree of neuropathy. The more you…

Dr. Powles: I’ve got a lady in her 80s to just zoom through this, which I thought was really odd. She’s still going on and I mean she’s amazing. She’s from Eastern Europe originally, came to the UK. I worked…

Dr. Grivas: It’s unpredictable

Dr. Powles: I thought, “Oh God, we’re going to really struggle. She’s about 45 kg,” and she went straight through.

Dr. Gupta: I have a patient who’s had bulky retroperitoneal nodes. After initial NMIBC [non-muscle invasive bladder cancer] 5 years later presented with bulky nodes, put him on EV-302 and he’s now 2.5 years out done with pembrolizumab. CR [complete response] after the first scan, I could not believe that was his scan and he’s cruising through all. I have to find reasons to not give the EV to him.

Dr. Grivas: Because they’re doing so well. It’s unpredictable, to your point, and some patients do great, but I think the educational part is key.

Dr. Powles: Super important.

Dr. Gupta: And skin exam. When patients come to my clinic, I do a skin exam because in my experience patients always under-report things when they are benefiting from the treatment, especially drugs like EV. But for chemotherapy, every little thing is over-reported. I make them walk for the gate because motor neuropathy is also under reported.

Dr. Powles: Sensory and motor accumulating with time, and if you treat through neuropathy you get into a lot of trouble.

Dr. Grivas: Absolutely.

Dr. Gupta: I just saw a patient 3 days ago treated in the community with EV monotherapy and she came in, her skin was peeling and she was still getting EV. They just told her to put that steroid ointment.

Dr. Powles: I don’t like that.

Dr. Gupta: I think that it’s so important because that was so worrisome even to me.

Dr. Grivas: To prep to your point Shilpa, the patient upfront, Tom, to your question, before you start the combination or EV alone, to prep the patient say that we might at some point dose reduce or hold or adjust and that’s okay. You set the expectation upfront. The other important point Tom, that I think you mentioned already that in addition to education of the patient, also education for the team. Our APP [advanced practice provider], our nurse, our pharmacy, because the team that manages that patient, I think the other point that you made, it will be a great time going forward to do de-escalation trials. To answer your question Shilpa, how much EV we need? I think it was the right design, Tom, to have EV at least until progression toxicity for this trial. But going forward I would love to see the escalation trials to evaluate how much we need.