Considerations for the impact oral hypomethylating agents will have on accessibility in myelodysplastic syndrome, as well as the importance of patient adherence.
Amer Zeidan, MBBS, MHS: The dosing is quite similar. It is 5 days, so you are giving the oral version versus IV [intravenous] version. The patient will take the pill for 5 days in a row. However, that does not have to happen in the clinic, so the patient could technically be seen on day 1 of each cycle; the patient gets the drug for 5 days compared to having to come for 5 days in a row for the IV decitabine. The pill is given once a day, so it is quite convenient for many patients. The dose that was used in the clinical trials is 35 mg of the decitabine in the oral version in combination with 100 mg of cedazuridine. That was pharmacokinetically equivalent to the 20 mg of the IV decitabine that we use currently.
Bart Scott, MD, MS: There have been a lot of studies that looked at the oral route of administration of different types of agents versus the IV administration of different types of agents. In regard to the oral administration, adherence if anything, might be better or improved because patients don’t necessarily need to travel to receive the agent; they can take it at home. No doubt, adherence and compliance will not be 100%; it never has been. It’s always important to think about the differences between the clinical trial and actual clinical practice. There have been multiple assessments of that, and it’s been clearly documented that patients who participate in clinical trials have better adherence and compliance rates than patients who do not.
There is a wide variety of reasons for that, and it’s not surprising. There are socioeconomic issues in regard to who would participate in a clinical trial: those patients tend to be more motivated. When we extrapolate data from the ASCERTAIN trial, we need to be careful in regard to how this might be applicable to a broader population of patients. It’s fair to say that there could be potential issues with compliance in a broader population of patients who are not necessarily participating in a clinical trial.
Amer Zeidan, MBBS, MHS: Oral dosing for any kind of chemotherapy is more ideal because of the issues we discussed. It's more convenient for the patient, there are less frequent clinic visits, and it doesn't need IV access. The main issue is that you have to have a very reliable and compliant patient who we know for sure is going to take the drug at home because, unlike the IV decitabine where the patient is being directly observed that they are getting the drug, you have to rely on the patient. Good education and explanation to the patient, and using other ways to make sure the patient is taking the drug, such as daily reminders, or some other ways, are going to be important when using these oral versions. That applies to all types of chemotherapy.
The second consideration with those agents is cost. Each time with the use of oral agents, there could be different insurance plans. Most of those patients are under Medicare, and oral agents are being managed under Medicare Part D. Part D could require a significant co-pay from the patient, while the intravenous use is under Part B. That would be an important aspect to address with the patients, making sure that the use of oral agents is not going to result in significant cost-sharing burden of the patients, which might compromise their willingness or ability to do an oral version. That’s also an important policy issue that has to be regulated by different agencies because patients should not be punished for choosing an oral version by having to pay much more out of pocket compared to an IV version. But that’s something that we have to see as the drug goes through the regulatory process.