Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Perspective on using immune checkpoint inhibitors as first-line therapy for metastatic UBC
4:37 minutes.
TRANSCRIPTION:
DR LOVE: So the question is — and this question was obvious from the first time people started even hearing about responses, before there was even any data, which is: Given that you do have — particularly in bladder cancer — an older population of sometimes frail patients, kind of putting aside the reimbursement or cost or regulatory issues, when you look at what we know right now and what your clinical experience is in terms of the risks and the benefits and the chances of response, do you think that we should be using checkpoint inhibitors up front now, or should we have more data? DR PLIMACK: So my opinion is that we need more data. I think we should use checkpoint inhibitors where they work the best. And I don’t think we know for sure that they work the best in the front line. Chemotherapy has its own set of issues but can work beautifully for some patients. We have had complete responders to chemotherapy. And so I think patients should get the benefit of all the different treatments we have. The response rate, believe it or not, to chemotherapy in the front-line, cis-ineligible setting, comparable to the front-line trials we’ve seen with PD-1 inhibitors, is higher: 36% with chemo compared to 24% with the PD-1 and PD-L1 inhibitors that have been tested in that space. So I just think right now we’re looking at only single-arm data. We’re looking only at the cis-ineligible population so far, right? My position is that we need more data and these may work better second line, and that’s where we should use them. DR LOVE: So do you think that in patients who are cis ineligible, for example, from renal dysfunction, do you think there checkpoint inhibitors should be utilized first line? DR PLIMACK: Yes. That’s a very good point. And I think we struggled with this on the Prostate Cancer Guidelines Panel when abiraterone, for instance, was postdocetaxel for a short period of time, right? What about the patient who we would never give docetaxel? Correct. I do not think someone should necessarily go to hospice without a chance at one of these PD-1 or PD-L1 inhibitors, if they’re a candidate for it and we think they can help them. So in that regard, it is a little tricky in terms of eligibility or ineligibility. DR LOVE: What about carbo-based therapy first line as opposed to a checkpoint inhibitor? DR PLIMACK: So carbo’s allowed. All of these agents are postplatinum. It doesn’t specify cisplatin. DR LOVE: No. But what I’m saying is, what do you think is a better choice, a carbo-based regimen up front or a PD-1 antibody up front? DR PLIMACK: I give carbo-based regimens right now, because that’s where the data is and that’s where the approval is. We also do it as part of a clinical trial, so we have clinical trials available front line combining chemotherapy with the checkpoint inhibitors. So I guess we’re a little different in that regard. But right now, the drugs aren’t covered front line. And so that’s one issue. And I think the data is coming. We’ll see it. But with the lower response rate with the PD-1 inhibitors, I’m not 100% sure that that’s the best sequence to go with. DR LOVE: So again, I’m thinking about the model — for example, we’ve seen this in renal cell. We’ve seen this with melanoma. I know it seems weird, but it kind of reminds me a little bit of, say, a BRAF-positive melanoma where the patient’s asymptomatic, doesn’t have a heavy volume of disease. And, at least in the past, people would go with immunotherapy, even now might go to immunotherapy. The idea is, they’re asymptomatic. We can try, see if they’re a lucky one and get the response. What about that strategy in an asymptomatic patient with metastatic bladder cancer? Try the checkpoint inhibitor. If it works, maybe they get a long response. DR PLIMACK: Yes, you could. You could certainly argue that point. I think you still have to tell them there is a risk of bad toxicity with the PD-1 inhibitors. And although it is uncommon, when it happens it’s much worse than really anything that we cause with modern chemotherapy and modern supportive care, right, so pneumonitis or colitis requiring steroids. Again, the chance of that is low, but in every trial with every PD-1 inhibitor, we’ve seen a collection of patients with Grade 3/4 toxicity. So you have to balance that along with the promise that you may have a good response. Right now, the only approved drug is atezolizumab. And the response rate to atezolizumab in the second-line setting is 14%. In the front-line setting, it’s 24%. So most patients actually won’t benefit from it. And if they have a better chance of benefiting from it later, am I doing it wrong, doing wrong by them by giving them a PD-1 first, where they may have less of a chance of a durable response versus giving it later? I don't know. |