Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Activity and tolerability of the recently FDA-approved anti-PD-L1 antibody atezolizumab for advanced UBC
4:38 minutes.
TRANSCRIPTION:
DR LOVE: So at that point, he actually did get a checkpoint inhibitor, I see. What happened? DR GALSKY: So he was treated with atezolizumab. And by the time he initiated that treatment he really was having more burden-related symptoms, was having pain, was having fatigue, some decrease in appetite. And I initiated treatment and, within about 2 cycles, clinically it was clear that he was feeling better. His pain decreased. His energy level increased. He was more active. And he continued on treatment. And after cycle 6, his initial restaging evaluation after starting treatment, there was already some reduction in the size of tumor. But, interestingly, over the next year his areas of measurable disease continued to decrease slowly — very interesting response kinetics and really not what we’re used to seeing with cytotoxic chemotherapy. DR LOVE: And so what’s his current situation? DR GALSKY: So he received his 40th cycle of treatment this week. DR LOVE: Wow! So he’s been on treatment for more than 2 years. DR GALSKY: He’s been on treatment for more than 2 years, tolerated it really quite well. He’s developed a rash, which has been managed at times with topical steroids. Other times he doesn’t require any management of the rash. And really that’s been his major adverse event. DR LOVE: Can you talk a little bit more about where exactly he had the rash? And I hear a lot about rashes with checkpoint inhibitors as being not really a big deal but very common. Is that the case? DR GALSKY: That’s been my anecdotal experience as well. His rash was on the face, erythema, in a distribution on his cheeks, and he also had some scattered erythema on his arms and legs as well, mild itching. And that’s been characteristic of other patients that I’ve seen as well — not necessarily the face, but this mild erythema, mild itching that occurs on the body and the arms and legs. DR LOVE: Any preemptive dermatologic measures you take in these patients? DR GALSKY: Given that the rash has not been bothersome for the majority of patients that I’ve treated and that even when it does develop we oftentimes don’t treat it and, if anything, use a topical steroid, we haven’t been pursuing preemptive management. DR LOVE: So this might be a good time to take a step back and talk about the data that we have on checkpoint inhibitors. Obviously, atezolizumab now is approved in bladder cancer. Maybe we can start out with that in terms of — first the mechanism of action, because it’s actually anti-PD-L1 as opposed to PD-1. First of all, what does that mean to you? DR GALSKY: So atezolizumab is an anti-PD-L1 antibody. Of course, I look at PD-L1 and PD-1 blockade as really blocking 2 components of the same interaction, really. If you imagine 2 people shaking hands, you’re blocking 1 arm or the other. And so from a mechanistic standpoint, I’m not sure that there’s the anticipation of so much in the way of difference, with the exception of being the potential importance of other ligands binding to PD-1, such as PD-L2. And, of course, if that is important, then blocking PD-L1 allows the PD-L2/PD-1 interaction to remain intact. And one could postulate beneficial effects from that or potential detrimental effects, and that’s really where the clinical data has to sort that out. DR LOVE: And just to be clear, if I understand it correctly, anti-PD-L1 binds with the PD-L1 ligand, but anti-PD-1 binds the receptor, which, as you said, would be involved with both PD-1 and PD-2? DR GALSKY: That’s right, with both PD-L1 and PD-L2. DR LOVE: And I’ve heard it said that there’s a thinking that maybe there would be less toxicity with anti-PD-L1, specifically pulmonary toxicity. I don't know if that actually has played out. DR GALSKY: So I think that that certainly was postulated initially as these trials were getting up and running. And if you look at the data, it really doesn’t provide a strong signal in support of that. |