Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 905: CC-486 (oral azacitidine) in patients with hematologic cancers who received prior treatment with injectable hypomethylating agents
4:37 minutes.
TRANSCRIPTION:
DR STEENSMA: This agent, CC-486, is an oral formulation of azacitidine. And why an oral formulation of azacitidine or of decitabine, which is also in development, are attractive are that, first of all, it’s more convenient for patients. Many of these patients wouldn’t have to come to the doctor nearly as frequently if they were getting injectable aza. The second attractive feature of an oral agent in this population is that you can explore other schedules that just wouldn’t be feasible with an injectable hypomethylating agent. For instance, you could give a low dose of the hypomethylating agent every day or for 21 days out of 28 days per month. And that might give you some of the benefits of hypomethylation, if that is how this class of drugs is working, for much more of the treatment cycle. DR LOVE: What was presented here? DR STEENSMA: So this was a multiple-center study. And that was the difference from what’s been presented with CC-486 before. Guillermo Garcia-Manero, it’s incredible what he’s able to do, get so many patients on study at MD Anderson. But this was a multicenter study that Guillermo led. And so they had 40 patients who had previously received a hypomethylating agent. Most of them had MDS. Twelve out of the 40 had AML. And then they were given the CC-486. And the response rate in the patients who were refractory to prior hypomethylating agents was 38%. And the overall response rate was 35%. And the drug was pretty well tolerated. It induced some of the kinds of things that you would expect with injectable hypomethylating agents, such as cytopenias. And there were a few febrile neutropenia episodes and some gastrointestinal adverse events, but not different from what you would expect with azacitidine injectable. So I think that this agent has, certainly, a chance of regulatory approval. Where we would use it, I think, we’d have to think about that long and hard. Would it be a replacement for azacitidine? We don’t have a survival study with CC-486 the way we do with azacitidine, with the study that Pierre Fenaux published 8 years ago. So we’d have to take that into consideration. But if you had a patient that lived quite a distance from the oncology center or wanted to avoid trips to the infusion unit, this is a very attractive approach. I will also mention that there is a combination of decitabine, fixed dose, with a cytidine deaminase inhibitor, which prevents it from being broken down in the gut and in the liver with first-pass metabolism. And we saw an abstract presented at the annual meeting that showed that the pharmacokinetics and pharmacodynamics were identical to this oral formulation compared with injectable decitabine. So that potentially could be in the mix as well. DR LOVE: Do you think that these agents should be — I mean, I’m not really asking from an FDA perspective. But, I mean, would you like them to be available? Would you utilize either one of these? DR STEENSMA: I would. If these were available, I would use them on a case-by-case basis. But I definitely, for older patients where our treatment is primarily palliative, I would use them in lieu of the injectable agents. There are going to be insurance considerations with an oral agent. If these are very expensive and a patient has Medicare that covers well the injectable agent but not the oral agent, that might affect which one we use. And I really would like to see some exploration of longer schedules with both of these agents to see if maybe we could do a better job by reducing methylation for a longer time. |