Pharmacy Times interviewed Allison Adekanye, PharmD, and Fallon Henkel, PharmD, BCOP, pediatric oncology pharmacists at Yale New Haven Health, about the treatment landscape and role of the pharmacist in the pediatric sarcoma space. Both Adekanye and Henkel emphasized the lack of major treatment advances in this space over the past 30 years, noting that more funding and research is necessary. They also discuss how the pharmacist’s role is crucial in the management of this disease because they educate patients and their caretakers, personalize supportive care, and advocate for patients.
Key Takeaways
- Limited Advancements in Treatments: Despite the different types of pediatric sarcomas, the primary treatment regimens have not seen significant changes in decades. The therapies for osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma still rely on traditional chemotherapy agents such as vinca alkaloids, platinums, and alkylating agents. Recent efforts to integrate targeted therapies have not yielded sustained success.
- Personalization of Treatment Plans: While initial treatment plans for pediatric sarcomas follow standard protocols based on diagnosis and risk stratification, there is room for personalization in the relapse setting and supportive care. This includes considerations for patient preferences, managing side effects, and individual needs such as antiemetic therapy, pneumocystis jirovecii pneumonia prophylaxis, and fertility preservation.
- Pharmacists' Role in Patient Advocacy and Education: Pharmacists play a crucial role in advocating for pediatric sarcoma patients by ensuring adherence to protocols, managing supportive care, and educating families about treatment plans and adverse effects. They are instrumental in personalizing care based on patient history and preferences, and in coordinating with other health care providers to optimize treatment outcomes.
Pharmacy Times: Can you introduce yourselves?
Allison Adekanye: Hi, I'm Allison Adekanye, I'm a pediatric oncology pharmacist with pediatric oncology and BMT here at Yale New Haven Hospital.
Fallon Henkel: And I'm Fallon Henkel, also a pediatric oncology pharmacist here at Yale New Haven.
Pharmacy Times: What are current treatment options for sarcoma and bone cancers, and how have they evolved in recent years? What do pharmacists need to know?
Adekanye: Yeah, sure. So I think the first thing to talk about is, when we're talking about pediatric cancers or sarcoma, it's not just 1 type of cancer, in pediatric cancers, there's about 30 different types of cancers. When people are discussing pediatric sarcomas, they're most likely talking about rhabdomyosarcoma—which is a muscle tumor—or one of the bone cancers, Ewing sarcoma or osteosarcoma, and all 3 of these are treated very much the same. They're unlike sort of "fancy" adult oncology, they're using very old school chemotherapy agents. We're using, [for example,] vinca alkaloids, platinums, alkylating agents, basically, the first chemos made...also, the therapy really has not changed in a very long time. So osteosarcoma, for example, the treatment's been the same since the 1980s and the last big trial was the EURAMOS trial, which was European and America's and it was back in 2003, and the backbone for that treatment has really been map, which is high-dose methotrexate, cisplatinum and doxorubicin (MAP). And same thing with Ewing sarcoma, vincristine, doxorubicin, cytoxan, again, like sort of all the same agents. And...in terms of treatment for rhabdomyosarcoma, the biggest change over the past 10 [or] 11 years that we've been practicing is really just the dose of cytoxan, so it's really not about adding new agents, but [instead determining] which dose is the optimal dose. And in that disease state, really the biggest change has been about the risk stratification, which then just determines which dose of cytoxan you're going to get.
I think [what] pharmacists [should] know about these sarcomas, the main takeaways are is that there's really been no major advances in the treatment of these sarcomas in the past 30 years. Another thing is that localized and metastatic disease, for these disease [states] are treated the same, so it's not like if you have a localized disease, [for example,] you get less treatment like you do for a lot of other cancers, they're both treated exactly the same. And there have been studies over the past 30 years trying to focus on targeted therapy, but they've not had any sustained success, so even though they have trialed agents here and there, there's really just been nothing that's panned out as actually being beneficial.
And another [thing] to talk about when you [are] talk[ing] about the treatment of pediatric sarcomas, is that surgery and radiation are almost always part of the treatment plan as well, and surgery is never a curative option alone. So, surgery is pretty much the mainstay for all 3 required up front, but you will always need chemo as well.
Pharmacy Times: How are treatment plans personalized for patients, and what is taken into consideration when tailoring these plans?
Henkel: There definitely is personalization that occurs based on a patient's disease state, but for the most part, it's we follow the Children's Oncology Group protocols, and those are divvied up mostly based on just diagnosis and risk stratification, so there isn't a lot of personalization in terms of the upfront therapy like Allison was just saying. It's pretty standard, but there's definitely room for personalization in the relapse setting based on goals of care, so those are important conversations to have with families, whether they want to take an oral medication at home, or they want to come into the hospital a couple days a week, things like that...
There's a little more personalization in terms of the therapy, but there is room to personalize supportive care for patients. So, one big one that most people think about off the top of your head is nausea and vomiting, so antiemetic therapy is personalized based on a patient's preference. If they've had chemo in the past and they're getting chemo for the second time in a relapse setting, a lot of times, they'll have a lot of anticipatory nausea, so that's something that we have to think about up front. There's personalization for other types of supportive care, like [pneumocystis jirovecii pneumonia] (PJP) prophylaxis, most people know that [sulfamethoxazole/trimethoprim] (SMZ/TMP, Bactrim; Roche) is the gold standard, but even in there, some younger kids want liquid versus tablets, and if for some reason, they have an allergy or they can't take [SMP/TMZ], then all the other PJP options you can kind of tailor to a patient. So, whether it's a daily med, like atovaquone (Mepron; Evonik Industries) or dapsone (Aczone; Almirall, LLC) versus pentamidine (Nebupent; Fresenius Kabi USA), which is monthly, and you prefer that patients could get inhaled pentamidine for the PJP prophylaxis, but there's some small kids that can't sit there and actually take deep breaths. So, those kind of things are [examples of how] pharmacists are involved in terms of personalization or chemo.
Other options or things we discuss, [for example,] options for fertility preservation, those are always important conversations and sometimes the attendings when they're working with a patient might forget that, so that's another thing that pharmacists can bring up on rounds or with the family as appropriate. And then, whether the patients get their chemo in the hospital or in the clinic setting, those are other things that we can personalize based on whether we feel patients [are] able to take enough oral liquid at home, or how old they are. Sometimes [with] little babies, you can't force them to drink anything, so those patients might need to be admitted versus given their chemo in the clinic if we can't really trust that they'll get a certain amount of volume per day.
Pharmacy Times: What are the pharmacist's responsibilities when helping patients with sarcoma or bone cancers?
Adekanye: Yeah, I think the biggest role as a pharmacist that we can play in the patient's treatment is being an advocate for the patient, or being aware of where they are in their therapy. I know here at our treatment center, [patients are] in and out, they see different providers so often that even though they have their own primary provider, it can sort of get lost. [For example,] what day are they on, what are they due for, what are they coming up for next, do they meet the requirements, like the ECOG requirements of organ function, do they need an [echocardiograph]? Lots of times, as a pharmacist surrounding inpatient, if [patients are] in for 1 cycle, I'll know next cycle they need an echo, we can get that and order it now so that we can be prepared, or a hearing test, or something like that. Also, knowing the protocols inside and out, and knowing what merits dose modifications so that when the patient does come in, sometimes, I feel like it does sort of fall on us that we might see something that the provider may not notice or may not think about as much, and we'll say this requires a dose modification or the supportive care agent is not okay with this drug.
The other thing too, with these sarcomas, particularly, is the timing of radiation and when they get [it], because agents like doxorubicin and daxcinomycin can cause what's known as radiation recall—which is basically like a sunburn, sort of at the site of the radiation that happens afterwards—so the protocols are built that if you start on day X with radiation chemo that day, and then you don't get those agents for about 6 weeks. But not everybody gets their radiation on day X, they might get it on day A, or on day Z, and being aware of that and then moving the plan as needed so that you, A) don't give the drugs when you're not supposed to give them, and B) that you do make up those drugs when they are needed. So I do feel that we play a very large role in just being aware of the overall treatment plan, where [patients] are in their plan, and what they need and when.
Then I think the other thing too is just being aware of patients as we get to know them, being aware of what their [adverse events (AEs)] were. What were their really big AEs were to the chemo? Is this a kid that gets really, really nauseous no matter what we do? Does this kid like [ondansetron (Zofran; Pfizer)], or does this kid like palonosetron[(Aloxi; Eisai Co, Ltd)], things like that. We sort of know our patients really well, so have enough of a smaller population that we can sort of either know that on the top of our heads, or we keep notes on them. So, I'll know if, [for example,] this patient needs to have their dextrose taken out of their hyper hydration, because they always have hyperglycemia...things like that, I think, are important because as the pharmacist on the team, we're one of the one main, consistent people...and so just being able to be there, sort of as an advocate for them.
Pharmacy Times: How do pharmacists educate and advocate for patients and their caregivers?
Adekanye: Again, I practice inpatient, and with sarcomas, a lot of the pediatric sarcoma treatment plans are inpatient because of the fact that they are getting hyper hydration and, you know, you can't make a little kid go home and know they're going to drink a liter like we can with the adults. So, even though sarcoma treatment in adults is mostly outpatient, we're still seeing a lot of those treatments inpatient for our kids, or even kids just don't tolerate well when they go home with nausea and vomiting.
So, I'm around daily, I'm able to help educate the family. I think another thing too, when you think about pediatric care, is that it's not just the patient that we're teaching, it's the family, and so, whoever that main caregiver may be, it's also them. So [we're] speaking with them and knowing, okay, what happens when you go home, what are you dealing with when you go home in terms of AEs, how can we help you with that? Also, sort of being a voice to say what the expected AEs might be, or what we're monitoring for when they're inpatient. Also, I think, in terms of adherence to protocol, knowing the parameters for clearance for methotrexate and being able to have that information and know it up front, so that when they're asking, "Oh, when do we get to go home?" you can already kind of know [they] have to meet XYZ. Also knowing when the levels need to be taken, I think, another important part of the pharmacist too—at least here at our institution—is once someone comes in for their chemo on day 1, on day 2, checking the MAR and making sure that the times are all correct, that the rescue medications are down for the correct time, that they line up accurately, that the nurses are aware, and then also [knowing] the patient's aware of what monitoring [is] going to beginning while they're here.
Pharmacy Times: Is adherence ever an issue in the pediatric population?
Henkel: [As far as adherence] in sarcomas, it's less of an issue than in other types of cancer because most of it is on-site, whether it's in a clinic setting or just because this is pediatrics, and I always think in terms of caring methotrexate, we have certain teenagers that are really gung-ho, and they're like, "I'm gonna beat my time from last time and try to drink more fluid!" And, you know, it's pediatrics so they kind of have to play little games with themselves to keep them motivated. But in terms of adherence to taking orals or anything like that, that's less of an issue in sarcomas then [other disease states.]
Adekanye: Yeah, I'd that say too. I think it's more in our...adult [or] young adult/adolescent population, where maybe they might be more like sort of...rebelling about wanting to take their meds. I mean, in sarcomas, we don't see that too much, but we do see in terms of adherence issues, [there are] pediatric patients that need to learn how to take pills or how to tolerate medication.
So again, in sarcomas, it's not too much of an issue, because there isn't really a lot of oral chemo agents that kids are on for pediatrics, because that's still not really part of the therapy for us like it is for adults. But just with supportive care and things like that, so working with ChildLife, working with the parents to help them and give them tips and tricks on how to get their kid to take the 5 mils of whatever medication they need to take.
Pharmacy Times: Are there recent or upcoming clinical trials in this space? What do you hope to see researched in the future?
Henkel: Like we said, for the majority of our patients, we're still using standard chemo, but there is some promising information with targeted therapies, and 1 place that we have seen some success is with larotrectinib (Vitrakvi; Bayer Healthcare Pharmaceuticals) and NTRK fusion sarcomas, so those patients actually are getting an oral agent up front which isn't a large part of our population, but it is 1 and it's progress so, we're hoping to be moving in that direction soon with more targeted therapies.
Adekanye: We've seen things like crizotinib (Xalkori; Pfizer) for rhabdomyosarcoma, for [fusion]-positive markers. There is a new osteosarcoma trial that is open now, but the backbone is the same as what we've had for 30 years, and then they're adding an oral agent, cabozantinib (Cabometyx; Exelixis, Inc.)—which I believe, a MEK inhibitor—and so, adding that to see if that has any benefit, whether they give it pulsed or separate. But again, I think it's a lot of trial and error, we've seen a lot of these agents be tested up front for pediatric patients and not having a lot of success with them.
But I think the biggest excitement for me, or what I would like to see the most coming out, is the chimeric antigen receptor (CAR)-T practice. So, there are a lot of CAR-Ts coming up for solid tumors, we actually had a metastatic rhabdomyosarcoma patient who was able to get CAR-T for his rhabdo and has been disease-free [for many years now]. So, I think that's a very exciting area. We've had so much success with our leukemic patients that it would be really great to see something like that for these kids.
Pharmacy Times: Any final or closing thoughts?
Henkel: I think the most important thing we wanted to bring up is that pediatric oncology is made up of 20 [to] 30 different types of cancer, some are more rare than others and some we see all the time, but there's just not of funding for pediatric cancer research just because of the small population. And we already have a small population, and then with so many different types of cancer, it just doesn't get as much promotion as I think a lot of other types of cancers.
But in terms of sarcomas specifically, we seem to be following what the adults are doing trial and error, so once we see something work in adults, then we kind of take that on, so, it's unfortunate, but it's just the nature of the beast in terms of our population [and the] amount of patients that we have.
Adekanye: I think too, the fact that a lot of the safety studies and phase 1 studies have to be done on adults just because pediatrics are a specialized, protected population, so, we have to wait for those studies to come out and then for the phase 2 [and] phase 3 adult studies to come out before we can really start our own phase 2 studies. And then, in terms of when we talk about the relapse setting, there is a lot of space to be able to use some of those adult agents that have been proven to be safe, but don't have labeled indications yet; however, again, with pediatrics, dosing, dosage size, and dose formulation is a huge problem. A lot of the oral chemo agents are only available as pills or capsules, and that could present a big problem when you have a small child that you need to treat and either can't swallow, or a lot of [the medications] you can't even open them because they're caustic. So, in the future, having universal formulations that everybody could take would be really great.
