Case 4: Multiple Lines of Therapy in Recurrent Bladder Cancer

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Arlene O. Siefker-Radtke, MD:It sounds like this is one of these challenging real-world cases that we’re starting to see more with clinical trials, patients who actually haven’t received chemotherapy. Now he has neuropathy as well though, from the enfortumab vedotin. I guess I’ll ask you, Tian, any thoughts as to what you would do for this patient?

Tian Zhang, MD:I think this is a really challenging case. And as you say, a real-world case that we’re faced with in clinic, and they’re progressing on multiple lines of active therapies in urothelial cancer. Probably in these situations I would think about other chemotherapy options. So could a dose-reduced docetaxel make sense for this patient or even vinflunine?

Could we give him some single-agent gemcitabine, for example, since he does have the chronic renal insufficiency, and controlled disease? And then I would also try to work a little bit more on his neuropathy. There are many things that we can do to make that better before we start a more neurotoxic agent. But very challenging, and often in these cases I’m going to our phase I clinical trials office and saying, “What do we have open this week?” And really trying to look for trial options for these patients.

Arlene O. Siefker-Radtke, MD:Would you ever add in carboplatin for a patient like this to your gemcitabine?

Tian Zhang, MD:I think depending on what his renal function is, what his estimated and real 24-hour creatinine clearance is, I think it’s certainly an option to retry. I had some refractory patients in my practice who have had some disease stability with rechallenge of chemotherapy options even in the 5th, 6th line with docetaxel. And so I think there’s still a space for that in the refractory chemotherapy, but it’s hard to select the right patients who will tolerate it.

Arlene O. Siefker-Radtke, MD:How about you Betsy? This was your case, what did you do?

Elizabeth R. Plimack, MD:Gemcitabine is a very active agent in bladder cancer. We are using less of it I think, especially at centers that use dose-dense MVAC [methotrexate, vinblastine sulfate, doxorubicin, cisplatin] as the frontline cisplatin-containing regimen when there are multiple subsequent options like the PD-L1 [programmed death-ligand 1] and PD-1 [programmed cell death protein 1] inhibitors, and others that we’ve just talked about.

But this patient hasn’t seen it yet, and so I think that’s something that’s worth trying, with the caveat that unlike his great response to pembrolizumab, if we get a response they aren’t necessarily going to be able to continue treatment indefinitely due to toxicity.

Your question about carboplatin is a really good one, because generally gemcitabine is given with carboplatin, and that’s where it sort of sits in the guidelines. In this particular patient with comorbidities and advanced age, I tend to do a layered approach where I try 1 and see how they do, and then add another if I need it. But again, that’s not evidence-based. I wonder if any of you would consider the same?

Arlene O. Siefker-Radtke, MD:Well, 1 option that we’ve used at MD Anderson Cancer Center is gemcitabine with doxorubicin. Now I don’t think that would be a great option for a patient with congestive heart failure, so I’m going to assume he has a cardiomyopathy. But we did publish some data with a triplet of gemcitabine, Taxol, doxorubicin in the frontline setting, which had a response rate of, I think it was 40% to 50% frontline, cisplatin ineligible using the typical Cockcroft-Gault formula less than 60.

Now again, he has neuropathy as well. So I always feel a little nervous or concerned giving taxanes. We’ve actually used a little bit of the gemcitabine, vinflunine that was published for lung cancer back in the day. I don’t know if they use it much anymore. But vinflunine has less neuropathy potential compared to other agents. So for a case like this I might, if I can get insurance to approve it, maybe I would consider gemcitabine, vinflunine, although I might start at a lower dose just to make sure he can handle it since he sounds like he’s a bit frail.

Transcript edited for clarity.