Case 2: Factors in Treating Cis-Ineligible Bladder Cancer

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Arlene O. Siefker-Radtke, MD:First, I wanted to ask Gordon. We have a patient who was presenting with metastatic disease and as often happens, they often have the CT [computer tomography] scan before the diagnosis. When would you go toward the bladder to make the tissue diagnosis versus the metastases?

Gordon Brown, DO:Well, I’m a urologist. I would at least go toward the bladder. But in all seriousness, Arlene, I think that oftentimes the medical oncologists, especially in our system, prefer to get tissue from the metastatic site as it relates to tissue typing and genetic analysis to maximally refine their therapeutic options. However, sometimes that sample is less than adequate, or more sample is required, in which case certainly we would go and resect this patient and get as much tissue as would be required to be suitable for any analysis based on the size of the tumor.

Arlene O. Siefker-Radtke, MD:Are you being referred patients who already have a tissue diagnosis but they just need more tissue for special stains?

Gordon Brown, DO:Yes, we are. And some of those things, oftentimes, will bypass us that have evidence of locally advanced or metastatic disease as identified by their primary physician or somebody else initiating their work-up, and will go right to my medical oncology colleagues. However, the challenge is, as it relates to that volume of tissue, we can overcome pretty quickly from a local therapy perspective. And we can also address their local symptoms if they exist, which is another piece of this here, which I think remains to be spoken about.

Arlene O. Siefker-Radtke, MD:Due to Dr Gordon’s thoughtful application of cystoscopy, we had copious tissue, PD-L1 [programmed death-ligand 1]—positive, no specific targetable mutations present. What do you think, Tian, what would you offer this patient?

Tian Zhang, MD:We’re discussing a metastatic patient now, ineligible for cisplatin based on his renal dysfunction. And so usually in this setting, I offer immunotherapy as a monotherapy. We now have 5 agents approved targeting PD-1 [programmed cell death protein 1] and PD-L1. And so the question and the label change that happened last summer really was around using PD-L1 positivity in this patient population. I think as we are seeing more from IMvigor130, the data that were presented last month at ESMO [the European Society for Medical Oncology annual meeting] really showed us that the monotherapy atezolizumab patients do better when they’re PD-L1—positive at baseline. And those patients certainly do better on the monotherapy than the PD-L1–negative. And so that really provides a framework and the data for which we saw the label change. So in this first-line cisplatin-ineligible patient, I do reach for our PD-1 inhibitors first.

Arlene O. Siefker-Radtke, MD:What do you think, Betsy, would you agree or would you do anything different?

Elizabeth R. Plimack, MD:I agree and I wouldn’t do anything different. I’ll speak to a couple of scenarios, not with this patient but that which we frequently see, and one is when they come to us, they have widespread metastatic disease, and we don’t know their PD-L1 status. So here we’re fortunate, due to your great collaboration with urology, that it was already sent, and you have it at your initial consultation. But often then we’re asked, should we just make our best guess and go with immunotherapy, or should we play it safe and go with chemotherapy, or should we wait? And that’s a common challenging decision that we have. Typically, if we can wait, I do. I’ll send tissue and try to wait so that we know and can choose immunotherapy versus chemotherapy. But in my practice, if there’s no time, we would start with chemotherapy with gemcitabine and carboplatin.

Arlene O. Siefker-Radtke, MD:OK. So luckily we have information first before having to treat.

Elizabeth R. Plimack, MD:Yes, always better.

Arlene O. Siefker-Radtke, MD:But I’m curious. What if this patient had extensive liver metastases, would that alter your chemotherapy choice or treatment choice?

Elizabeth R. Plimack, MD:I think based on the data, it shouldn’t, right? There are no clear data that having liver metastases, patients do poorly. Again, I think this speaks to the point of where you’re getting your biopsy though. I think in that case I would feel most comfortable treating based on PD-L1—high from a liver metastasis, so that I know that the clonal evolution didn’t deplete the PD-L1 status on the metastasis. But I’m always more nervous treating patients with liver metastases regardless really of what we choose.

Tian Zhang, MD:I think sometimes the location of that liver metastasis may impact my decision. If it’s really close to the common bile duct or something that looks like it’s starting to impinge, we may be trying to get to an earlier response, so that we avoid hyperbilirubinemia or biliary obstruction. And so in those patients, maybe we would be choosing chemotherapy first to try to get a response quicker rather than the immunotherapy.

Elizabeth R. Plimack, MD:Arlene, how do you approach liver metastases?

Arlene O. Siefker-Radtke, MD:Well, it’s a difficult choice at this point. Historical data have suggested the liver metastases patient doesn’t always respond as well to an immune checkpoint inhibitor. I don’t think we’ve done a deep dive into the IMvigor130 data to look at all the different subsets and of course, nor should we use those to provide definitive recommendations, although we all use them to try to guide us in our choices. Because we know if we pick the wrong strategy for a patient with explosively growing disease, they may not have time to get on a better treatment. So patient selection does matter.

I don’t know, if they had vigorously growing liver metastases, I might choose a chemotherapy regimen first, just because they grow quickly, and sometimes a single-agent immunotherapy is like holding a garden hose on a 3-alarm fire. We just can’t generate enough of immune response to make an impact. I’m certainly looking forward to seeing more of the IMvigor130 data to try to understand, are there groups where the benefit is greatest, node-only, which has typically had the best benefit overall from an immune checkpoint inhibitor? Or will we see in PD-L1—high that it’s still looking quite good in the setting of a liver metastases patient?

Elizabeth R. Plimack, MD:We’ll have to see.

Transcript edited for clarity.