Treatment Considerations With TROP2-Targeted Therapy

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Transcript:

Rasheda Persinger, MSN, AGNP-C, AOCNP: I have a couple of questions for Dr [Kevin] Kalinsky and Kayla [Freeman]. When you say the oral dex [dexamethasone] rinse with the saci [sacituzumab], are you treating it like…

I believe when I used to work in the breast space, you would do the oral rinse preemptively, or prophylactically with everolimus. Is that how you're doing the oral rinse?

Kevin Kalinsky, MD, MS: Correct. It is with dato [datopotamab], with Dato-DXd [datopotamab deruxtecan] that we’re using this. We have an adjuvant trial now with dato and the wording there is, like, strongly encourage an oral rinse in this because not all countries have access to the oral dex rinse. But we're utilizing it and it's the exact same as what you mentioned that we would give with everolimus [Afinitor].

Rasheda Persinger, MSN, AGNP-C, AOCNP: And then my other question is, with the use of growth factor, are you waiting for them to drop before you place it or are you preemptively starting them with the growth factor?

Kevin Kalinsky, MD, MS: I can answer and then Kayla [Freeman], feel free to chime in, but if we know that a patient has a history of low counts or required growth factors, we are prophylactically utilizing growth factors. If not, then we just give it a go. However, the rate of utilization of growth factors in the studies was about a third to 50% of patients required growth factors.

Rasheda Persinger, MSN, AGNP-C, AOCNP: Okay.

Benjamin L. Musher, MD: The teaching has always been you've got to let these drugs get out of their system and then give growth factor because of this theoretical, but I think never proven, possible damage to stem cells and blah, blah, blah. Even with these drugs that have a longer half-life, it's okay to do that, are you using the short-acting, are you using G-CSF [granulocyte-colony stimulating factor] or are you using the pegfilgrastim [Neulasta] and the longer acting ones?

Benjamin P. Levy, MD: Great question.

Kevin Kalinsky, MD, MS: So, Kayla, this is something that we are dealing with. I would say on a weekly basis what we are commonly doing—and Kayla, I don't know if you feel like you're seeing this in the other clinics with our colleagues as well—is we're giving the short-acting after day 1 and then the long-acting after day 8.

Kayla Freeman, DNP, APRN, FNP-C: That’s exactly what I'm seeing.

Benjamin L. Musher, MD: Meaning short-acting first for 6 days and then you give the long-acting?

Kevin Kalinsky, MD, MS: No, we usually do 2 or 3 doses after day 1 and then the long-acting after day 8.

Rasheda Persinger, MSN, AGNP-C, AOCNP: And is that more so because it’s insurance-driven? Because it's easier to get approved when it's a day 1/ day 8 treatment vs, if I'm not mistaken, pegfilgrastim needs a little bit longer time.I could be wrong with that.

Kevin Kalinsky, MD, MS: Yeah, a lot of our decisions, including the specific long-acting that we're utilizing, is insurance-driven.

Benjamin P. Levy, MD: The tox [toxicity] on Dato-DXd with the stomatitis is important, Kevin. We are participating and leading some of these studies and are learning about this unique toxicity. And Rasheda [Persinger] has helped out a lot with our patients on trial. Rasheda, do you just want to mention what we're seeing with this? The toxicity is not prohibitive, but it's something that has to be mitigated and something that we have to be very proactive about to get these patients through. Not all of them, but some of them, Rasheda, do you just want to mention the stomatitis with the Dato-DXd?

Rasheda Persinger, MSN, AGNP-C, AOCNP: Yeah, that's why I was curious to see how you all were addressing it because that is one of the biggest things. To be quite honest, I don't see a lot of these patients, so I don't seem to have a lot of information to provide as it relates to the toxicity. But one of the things that I can definitely remember is stomatitis and it's so persistent, and debilitating as it relates to the oral intake and so forth, which is so odd when I think of a target therapy. I'm not used to seeing so much of this stomatitis and this persistence regardless of what we typically use with the magic mouth rinse or the dupes magic [mouth] rinse. Whatever rinse you want to take, you know, it is still so persistent, which can cause other problems in terms of nutrition, weight loss, and so forth. So that's really the biggest thing. I can't remember, Dr Levy, anything else that really stands out when we're using this drug.

Benjamin P. Levy, MD: Yeah, I want to mention 2 things, which I'm glad. Kevin, the hair loss with saci, we don't see complete hair loss, at least in lung, with datopotamab deruxtecan. We don't see grade 3 or 4 alopecia in our patients… [CROSS TALK]

KevinKalinsky, MD, MS: We have not seen, I would say because even if we've been treating patients in a neoadjuvant setting with dato, we’ve not seen that everybody's lost their hair with dato.

Benjamin P. Levy, MD: Right. So, it's very interesting, once again, you've got 2 drugs that are TROP2 directed and have maybe a similar payload, not exactly, linkers are kind of similar, but one causes challenging stomatitis and the other does not. And the postulate from the Dato-DXd folks is, well, there's TROP2 expression on the oral mucosa. Well, if that were the case, then I would hope and I would think that sacituzumab would also cause this. So clearly the drugs are being metabolized differently. There's an extraordinary complexity with drugs delivered to patients, period. The other thing I would say is that with the stomatitis we're having challenges. We’re participating in some of these trials and the devil's in the details with what I'll say, stomatitis is something you can get the patient through, but you have to be proactive and the devil's in the details with management. So, we've been asked to compound the dexamethasone rinses. Believe it or not, Hopkins sometimes has a hard time compounding the dexamethasone rinses, so we have to go to the CVS or the Walgreens or whatnot to see if they'll do it. We live in a highly resourced area and we're sometimes having trouble getting this compounded. So, you know, it's an interesting phenomenon. I will say that not everyone has the stomatitis. And if you look at the data from lung, most of it is grade 1 or 2, so you can get them through it. But this is a new one for us.Kayla, you had a question?

Kayla Freeman, DNP, APRN, FNP-C: I was just going to add, with this stomatitis, I think it's imperative we're asking patients about whether or not they're having any irritation in their mouth, and, making sure they're using the dex rinse. I've had patients where they say, “Hey, I'm not having any problems right now, so I just stopped using it.” They'll tell me that [and then] I'll tell them [that] we're utilizing it prophylactically and encourage them to continue to use it.

Benjamin P. Levy, MD: Yeah. Good point.

Rasheda Persinger, MSN, AGNP-C, AOCNP: Can I also just add something about the stomatitis that, yes, we normally see grade 1 and grade 2, but if we look at grade 2, it can still cause some significant problems. You know, from our standpoint, it's like, oh, it's not a great 3 or 4, but from the patient's standpoint, grade 2 still has pain, and still alters and decreases the taste of certain foods. So although it’s still a grade 2 scientifically, it may to them be a grade 4.

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