A comparison of the safety and efficacy of orally and intravenously administered oncolytics.
Alison Duffy, PharmD, BCOP: Dr Steeves, what has been your experience with efficacy and safety of the oral agents versus IV [intravenous] in terms of best practices for improving patients’ adherence? Any differences that you specifically point out to patients with regard to administration?
Cody Steeves, PharmD, BCOP: I think for pharmacists, one of their biggest roles in these oral oncolytics is stressing how important adherence is. We have data from CML [chronic myelocytic leukemia] that will tell us how important it is; just a small decrease in adherence can lead to a large increase in the chances of losing your complete response in that disease setting.
I would imagine if we did the same data in CLL [chronic lymphocytic leukemia] they would show similar results. But we always know that efficacy and adherence go hand in hand. You’re going to have fewer hospital stays, less progression of disease, you’re not going to have to move on to another therapy, things like that, when adhering.
As a pharmacist it’s really important to educate the patients on this adherence, starting with the first conversation. I think this is one of the hardest things for a doctor’s office to manage. They can’t watch a patient swallow a pill every day. If a patient has 6 cycles of chemotherapy, they either came or they didn’t, so we know if they got their IV chemotherapy. But doctors can write a prescription for a 6-month supply of an oral agent and just hope and pray that the patient’s going to take it every day, and hope that the pharmacy can manage that accordingly.
So as a pharmacist it starts with the discussion of how important it is to schedule it, how important it is to call the pharmacy, call the doctor’s office, call your nurse, call whoever you need to if you’re having an adverse effect, and see if we can help to manage it, rather than just stopping the drug for a couple days on your own, or something like that, and try to avoid these holdups in therapy.
Efficacy data, I think, with all the agents are going to be pretty strong. It’s a disease that’s not extremely difficult to manage, in most cases, especially our IgHV [immunoglobulin heavy chain variable]-mutated, non-17p-deleted patients, but tolerability becomes a major concern.
Our frail patients, our patients with multiple comorbidities, are going to have a lot harder time. It’s going to be a little more dangerous to give them those higher concentration drugs. So the safety of giving those patients IV chemotherapy should always be discussed, and that’s why the NCCN [National Comprehensive Cancer Network], I believe, recommends not giving FCR [fludarabine, cyclophosphamide, rituximab] in those aged 65 and above, in those frail patients, and sticking to the oral therapies.
Additionally, when you consider the safety of the IV chemotherapy even in younger patients who may get the disease, maybe in their early 50s, and may have many decades of life expectancy still, some of the data have told us that they will increase their chance of secondary malignancies—not just nonmelanoma skin cancer, which we know is pretty well tied to CLL, but any secondary malignancies—by up to double, maybe 2.5 times in their future decades of life.
Then going to the actual administration of the 3 primary NCCN recommended therapies, they’re all different in their own right. Venetoclax is administered with food the same time each day. Acalabrutinib is BID [twice a day], so 12-hour spacing, and getting the patient adherent to that regimen is important. Ibrutinib is once daily and with a full glass of water, so keeping patients on track with adherence is very important.
Venetoclax has its own set of adherence challenges because they need to adhere to their doctor’s office visits if they’re not doing it in the hospital, so they can have TLS [tumor lysis syndrome] measured early the start of therapy. They all present their own unique challenges, and it again all loops back to the discussions we’ve had of patient-specific factors in choosing which patient is the best for a particularly therapy. I’d love to hear your thoughts, too.
Alison Duffy, PharmD, BCOP: I think that’s very helpful. I definitely agree with you. In terms of improving adherence, I think working with a patient early on to assess what’s worked for them in the past, what challenges they’ve had in the past, who helps them with their medications, how to incorporate that into their routine, has been a helpful intervention.
I know I’ve found that if I’m strapped for time, at least figuring out exactly how to customize that to the patient’s lifestyle has been helpful in my practice, and I think plenty of adherence studies in oncology or otherwise support that intervention alone can be really helpful. So I’ve latched onto that.
Asking patients the number of doses they’ve missed within a clear period of time, a week or 2 weeks, we found to be helpful, and that’s supported in the literature, as well. Then having the process in place to trigger what a problem is with adherence.
We usually use the adherence metrics from the CML tyrosine kinase inhibitor [TKI] data of 85% adherence, or 2 or more missed doses in a 2-week period, and building that into the adherence-tracking process, whatever that looks like, if it’s individualized or system-wide, can be helpful.
I agree with the oral administration differences. That’s one thing that I’ve found might get forgotten or missed in the large picture of education about a new stage or a new diagnosis. As pharmacists, I agree with you, a huge thing we can do is help patients with administration. Also with acalabrutinib, avoiding acid-depressive therapies because of that acidic environment for absorption.
The other thing that I think is challenging if we’re combining these therapies is what do the administration differences look like for oral versus IV therapies? And I think it becomes really challenging when there are so many different stakeholders that may be involved in one or both of those oral/IV dispensing processes, or insurance approval processes.
We try to figure out ways to create a clear communication plan, at least for the family and patients, so they know exactly what therapies they’re getting and when. Because as we already mentioned, the schedule and the duration and the frequency and the dosing for both agents, now that we’re starting to combine 3 agents in some of the trials it becomes really complicated.
That can throw some wrenches in there from a safety perspective, and an adherence perspective, too; appointments. It can get so complicated and be a huge stressor for patients that I think we can all help to try to alleviate.
Video link: https://youtu.be/_3D5j0jpFq0