Combination Immunotherapy for Advanced Bladder Cancer of Variant Histologies
Dr. Pal: Welcome to PracticeUpdate. My name is Monty Pal, and I’m a Medical Oncologist at the City of Hope Comprehensive Cancer Center. About a year ago, I finished the ASCO Leadership Development program, and one of my colleagues there was Brad McGregor who has just risen to great heights. He’s the Clinical Director of the Lank Center at the Dana-Farber Cancer Institute. Brad, it’s a delight to have you here today.
Dr. McGregor: Thanks for having me.
Dr. Pal: Oh, absolutely and you’re just killing it at ASCO this year. You have eight very exciting abstracts. One, in particular, is going to be featured in the poster discussion session here at this meeting, and I wanted to ask you a little bit more about that. This is a trial that pertains to nivo and ipi in bladder cancer, right.
Dr. McGregor: Correct. So, this is a trial that actually started a couple of years ago. It's not only looking at bladder cancer but actually looking at rare GU malignancies. So, when patients come to us and they have these rare tumors and really looking for something novel, a new treatment, and, unfortunately, most of these patients aren’t eligible for clinical trials. So we looked to develop a trial for those patients with a rare tumor, so that could be bladder cancer of varying histologies such as small cell, adeno-, urachal carcinoma, as well as adrenocortical carcinoma, and then sort of other tumors as well, penile carcinoma, treatment-refractory germ cell tumors, prostate cancer of varying histology, so really try to look at a trial to encompass all of these malignancies, and so this the extended report. The first cohort, which is the 19 patients with bladder cancer of varying histology.
Dr. Pal: Oh, that’s awesome. And tell me about this mix of histologies. What was the distribution, roughly speaking?
Dr. McGregor: Yeah, so, it was actually pretty well balanced across the spectrum. So, we had one plasmacytoid, but we actually had several urachal, adenocarcinoma, small-cell carcinoma, as well as squamous cell. So, there was at least three to four of each of those in the cohort.
Dr. Pal: That’s interesting. I’ve seen a lot of squamous in my practice. It’s so difficult to treat, but tell me, overall, what were your results looking like?
Dr. McGregor: Yeah. So, we actually, you know, even though with bladder cancer that using the high dose ipi, low-dose nivo, we did renal cell dosing. So, we did the low-dose ipi, high-dose nivo and we gave that for 4 cycles followed by maintenance nivolumab, and what we saw actually overall was a pretty impressive response rate at 37%, and this included 13 of the patients actually had prior treatment with chemotherapy.
Dr. Pal: Now, let me ask you. For the doc who’s out there in the community this data sounds really good, 37% response rate, very impressive, well beyond what I would expect for monotherapy with PD-1 or PD-L1. Is this ready for prime time?
Dr. McGregor: So, I think it’s something we have to certainly explore. I think, you know, this was just a small group of patients, 19 patients. I mean, certainly, a very intriguing result. Two patients actually had a CR at this point, and most of the patients who are responding are still on therapy, so that could actually improve over time. So I think what we need to do is probably expand this and look at, you know, a larger set, and that’s something we need to really explore because these patients really don’t have a lot of treatment options. Chemotherapy often doesn’t work for them and so to have something like immunotherapy with these response rates is something that certainly merits further exploration.
Dr. Pal: Very interesting, and tell me about those CRs, were they a particular histology or...?
Dr. McGregor: So, one of them was a plasmacytoid and the other one had just transitioned to a CR just this week. I believe it’s a small cell patient.
Dr. Pal: Very...and small cell. Wow, that’s impressive.
Dr. McGregor: And we actually saw responses in urachal and adenocarcinoma as well, so, this is not something that when we started out I thought, we were thinking that we’d probably see more responses may be to small cell to squamous. I’m just getting the data ready, but we actually saw responses in urachal and adeno-, so we’re actually doing correlative work at this point in time, looking at PD-L1 staining whole-exome sequencing to really try to get an idea for any markers or response in this situation.
Dr. Pal: Very interesting. You can learn a lot from that in just individual patients I’m sure, but when we’re talking nivo-ipi the subject of toxicity always comes up. So how was it in your cohort?
Dr. McGregor: Yeah. So, it was comparable to what we’ve seen with the CheckMate 214 data, so 25% of our patients required high-dose steroids, so comparable. Comparable to grade 3 toxicities what we’ve seen before. So, certainly, still a toxic regimen and it requires careful monitoring and early interventions, but it was manageable toxicities. We did, unfortunately, have one patient passed away from toxicities due to neurological autoimmune complications.
Dr. Pal: Got it. Got it. Well, I guess to sum it up, great response rate, perhaps, you know, some work to do in terms of weeding out the toxicity profile, but I’m excited about the genomic work. Brad, congratulations.
Dr. McGregor: Oh, thank you.
Dr. Pal: And that’s it today for PracticeUpdate. Thanks so much for joining us, and we’ll be back with many more interviews from ASCO 2019.
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