Immunotherapy Use in Advanced Urothelial Carcinoma - Episode 5
Transcript:Daniel P. Petrylak, MD: Atezolizumab has been approved, Rob. And what is your experience in treating patients with atezolizumab?
Robert Dreicer, MD, MS: At a high level, I would say not terribly dissimilar from what we saw on trials, but there are patients who would never have gotten the trial. I’m going to briefly describe a guy, and you all have seen somebody like this. He’s a young guy—and when I say young, he was 38 years old—with metastatic disease, nodal and bone metastases. When I saw him, he had a hemoglobin of 5 because he had a metastasis that was bleeding into his colon, as it turns out that was biopsy proven. He got tuned up a little bit, came back and had a hemoglobin of 7, but was in a wheelchair. Performance status was around 2.4. He had received carboplatin-based chemotherapy by his oncologist before he progressed with all these issues. Following 2 doses of atezolizumab, he walked into clinic and his hemoglobin was 12. He’s now been on therapy. He’s about 18 cycles out—working, hunting, doing all the things. He gained 55 pounds back.
This was a guy who I would have probably referred to hospice and symptomatic supportive care. And I don’t think it’s that unusual. This is sort of the poster child. So, to me, having these drugs is a paradigm shift. And, granted, it’s only 20% to 25% of patients. Most of our folks don’t respond. We’re going to talk more as the program goes along about how to make that number bigger. Hopefully, the point that Betsy made about maybe we’re getting responses from the same group, but perhaps by using different therapies or adding them together, we expand the group. This is the promise of immunomodulatory therapy in bladder cancer, and, to me, that’s what the community uses. Using these therapies now in the real world, frankly, has been encouraging because I see people respond who would never get on the trial.
Daniel P. Petrylak, MD: And I think the impressive thing is the durability. I think we’ve mentioned the durability. In fact, we updated our phase I experience at this meeting. And one of our patients is now 39 months out since the original treatment. He had had 2 prior chemotherapies. In fact, if you respond, you’re going to generally respond for a fairly long period of time. The median duration of response in the phase I trial, as well as the phase II trial, has not yet been reached. So, the responses are durable.
Robert Dreicer, MD, MS: Emphasizing that, again, we all know this because we live this life. But the fact is that other than the node-positive patients you could give cisplatin to that you do see—and all of us have a few of those patients, and maybe more than a few—the reality is, it’s a tiny fraction. Nobody else does that with the drugs that we have. This is a striking difference in how we take care of people.
Dean F. Bajorin, MD: We can state unequivocally, we never saw this before immunotherapy.
Elizabeth R. Plimack, MD, MS: In second-line.
Dean F. Bajorin, MD: In second-line therapy. I have a patient, one of the first patients on atezolizumab and who actually is in CR, progressed right through chemotherapy with disease in bone. He is one of the first patients on that trial who went out and bought a new boat and named it “Miracle.” And so, I think there’s a message.
Daniel P. Petrylak, MD: That’s certainly great. We need more of them. That’s what our goal is, to try and improve these treatments and make immune therapy more applicable to all patients. Rather than having one-quarter of patients, have at least 50% moving forward. We are developing new agents for this disease and, recently, nivolumab was approved for the treatment of second-line urothelial carcinoma. So, Betsy, could you go over the CheckMate-275 trial?
Elizabeth R. Plimack, MD, MS: So, we participated in this trial. This is another single-arm study. I think the hallmark of this study, it’s an awful lot of patients. It’s a high number of patients, 270, on this trial. I think it is a different agent, but is not necessarily a new paradigm. These were all checkpoint inhibitors. I think they all interfere with the same pathway, and I think it shouldn’t be a surprise that we see some consistency of data across these data sets. The duration of response, again, not reached, but speaking to durability was 20% overall response rate. That’s exactly where we’re hitting with all of the checkpoint inhibitors in this second-line space, and it’s not a surprise that it was approved because it does just as well as the others. This one is an every-2-week dosing schedule, and I think the dosing may evolve for nivolumab across the program over time, so we’ll have to watch for that. That’s one way that it stands out. The rate of adverse events was numerically maybe a little bit higher on this one. But, again, I think without randomization—certainly without randomization to chemotherapy or head-to-head comparison—it’s hard to draw correlations there. So, it’s another tool, but how it’s different, I’m not sure.
Daniel P. Petrylak, MD: Well, exactly. The differences also could be attributed to the heterogeneity of the disease. As you pointed out, it’s extremely difficult to compare one agent to the other in this particular setting, and probably there will never be a randomized trial that answers that particular question.
Transcript Edited for Clarity