Toxicity Management for T-DM1 and T-DXd in Breast Cancer

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Transcript:

Benjamin P. Levy, MD: Kayla, what are your thoughts here being the APP [advanced practice provider]? What are the different toxicities you may see or are there any differences in how you usher patients through T-DM1 [trastuzumab emtansine (Kadcyla)], or trastuzumab/deruxtecan [T-DXd]? Do you find one to be better than the other? What are your general impressions, having the clinical experience that you do with both drugs?

Kayla Freeman, DNP, APRN, FNP-C: I think with T-DM1, I probably see fewer adverse effects. Of course, we’re still monitoring for fatigue and the slight chance of a pneumonitis; we’re watching out for that. With T-DXd, though, we’re definitely seeing nausea with these patients, so [we’re] ensuring that their premeds [premedications] are bulked up or if we need to add additional meds. Fatigue, of course, [we’re monitoring for] and any interstitial lung disease [ILD]; [we’re] watching out for that risk as well. Those are the biggest things, I think, in comparison. But I think there are more adverse effects associated with T-DXd, for sure.

Benjamin P. Levy, MD: Can I ask a question? Rasheda [Persinger, MSN, AGNP-C, AOCNP] and I have got into this argument before, a healthy discussion. This is a true argument that’s happened a few times. How often do we need to get echocardiograms [echo] on our patients with T-DXd? Rasheda,…I tend to be a little bit more lenient and say they’ve [received] one, it’s a healthy person. Do we need them every 12 weeks? What are the data there? This is why I love these panels; I get to learn from people who actually use it more than we do. What are you guys doing at Emory [Winship Cancer Institute of Emory University, Atlanta, Georgia] with breast cancer? And Ben and Michal [F. Segal, RN], don’t worry, we’ll get to the gastric after lung because I want to hear what you guys are doing. But what is the usual monitoring for that?

Kayla Freeman, DNP, APRN, FNP-C: Every 3 months, we’re at least trying to get echoes on our patients…plus or minus. Sometimes they go a little bit longer. But due to the cardiotoxicity risk, we are trying to do it every 3 months because I’ve seen a patient getting a HER2 [human epidermal growth factor receptor 2]-targeted therapy and get the echo and their EF [ejection fraction] has dropped. Of course, it’s harder for patients [with metastases], especially if they’re responding very well. What do you do, if you do have a decline in their ejection fraction, especially when they’re doing so well? But every 3 months, typically. [CROSSTALK]

Benjamin P. Levy, MD: [CROSSTALK] OK, I guess Rasheda is right and I’m wrong.

Kevin Kalinsky, MD, MS: I thought you were also going to ask the question of how frequently we’re checking CTs [computed tomography scans] of the chest in patients who are getting T-DXd. I’m glad you didn’t ask that question. That’s a harder question for us.

Benjamin P. Levy, MD: Well, let me ask it. The ILD rate from our study was 5% and we do CTs every 12 weeks anyway like they’re water at our institution for lung. For monitoring for toxicity that’s different. What’s the threshold for breast cancer? It’s a great question. I don’t know what the ILD rate is for breast but clearly at 6.4 mg/kg in lung, 25% ILD rate all grades, most of them were grade 1 and 2. When you go down to 5.4 mg/kg, and we’ll talk about this in lung data, the ILD rate was much lower, less than 6%. So it’s there, and theoretically we’re starting to see this with this class. But what’s your threshold, Kevin, for when you’re seeing a patient who may be getting a little short of breath?

Kevin Kalinsky, MD, MS: For us, the rate’s about 10%. So we, in the studies, check CTs of the chest every 6 weeks. And commonly we’re scanning as frequently as you are, every 12 weeks or so. The other issue that has existed is that it’s not an adverse effect that we see right away. Patients could be on it for a year and then develop that toxicity. Kayla can speak to this too. There are some times that we check every 6 weeks, especially, of course, if somebody is having coughing or shortness of breath, then we’re prompted to do a CT earlier. But in the absence of that, sometimes I split the difference. I do it every 9 weeks. I’ve asked colleagues across the country and I feel like everybody’s doing something a little bit different. The way it was monitored in the clinical trial, doing it every 6 weeks, is not always feasible with patients. And patients don’t love doing as frequent scans as what was done in the trials. So sometimes we split that difference. But of course, for us, if it’s grade 2 or higher then we have to stop.

Benjamin P. Levy, MD: Kayla and Kevin and any others…I’m hearing monitoring echoes every 12 weeks, a low threshold for CAT scans to assess for ILD, but what about cytopenias? Are you seeing that? I’m just interested because we’re going to go tumor type by tumor type and combine these modules in the discussion guide a little bit.

Kevin Kalinsky, MD, MS: With T-DM1 we can see thrombocytopenia.

Benjamin P. Levy, MD: And you don’t see that with the T-DXd?

Kevin Kalinsky, MD, MS: No.

Benjamin P. Levy, MD: OK, and any other things… [CROSSTALK]

Benjamin L. Musher, MD: May I ask a question on the echo situation?

Benjamin P. Levy, MD: Yes.

Benjamin L. Musher, MD: We don’t use anthracyclines in gastric cancer anymore. Does prior exposure to anthracycline increase your risk at all? Are you more vigilant if patients have [received] T-DXd in the adjuvant or metastatic setting?

Benjamin P. Levy, MD: Yes, prior exposure to anthracyclines for sure increases the risk of cardiomyopathy.

Benjamin L. Musher, MD: Even if their echo or EF was fine when they finished anthracycline, before you start the ADC [antibody–drug conjugate]?

Kevin Kalinsky, MD, MS: Yes, there are reports of latercardiomyopathies due to anthracyclines. I will also say, though, that in breast cancer, for HER2-positive [+] breast cancer, we have really moved away from utilizing anthracyclines. It’s more applicable for patients with HER2-low disease because for a high risk of positive or triple negatives, we’re giving anthracyclines. For HER2+ breast cancer, it’s really less frequently that we’re giving an anthracycline.

Benjamin P. Levy, MD: OK, we’re almost done with breast. I have a few more questions. Backing up, T-DXd has shown survival advantage vs its competitor T-DM1. It is the preferred [drug] in HER2+ and we have data now on HER2 low. So the efficacy is there. You’ve got toxicities that you’ve mentioned with some cytopenias, and echocardiograms that need to be done to monitor cardiotoxicity, and we need to watch out with prior anthracycline. That was a good comment, Ben. Are there any other toxicities that you’re seeing? I have one more question, then we’ll [do] lung and GI [gastrointestinal]. How long do patients stay on this drug, in breast cancer? I mean, it’s a metastatic setting where patients live a lot longer in breast than they do in lung and I think in GI malignancies. How long are you keeping them on this and are there ways to keep them on it longer? Are you dose reducing or are you increasing the interval? How does that work?

Kevin Kalinsky, MD, MS: I can take an initial stab at this, and Kayla, feel free to chime in. For T-DXdin HER2+ disease, the median time that patients can be [receiving it] can be over a year and a half. For HER2-low [disease], it was about 10 months or so, understanding that this is representative of ER+ and ER-negative [–] disease. And in terms of dose modifications, when Kayla mentioned some of the toxicities like fatigue or nausea, it does seem to be dose dependent. So when we think about tolerability, if we’ve optimized our antinausea regimen and patients are still having a challenging time tolerating it, we certainly dose modify.

Benjamin P. Levy, MD: Kayla, do you have any other comments on that and getting these people through a year and a half of these drugs? Are there any other strategies that you are proactive about or do you find it that these patients are able to stay on drugs with these strategies of dose modification that Kevin mentioned?

Kayla Freeman, DNP, APRN, FNP-C: I think it’s just about optimizing supportive medications, as Dr Kalinsky already mentioned. And then, of course, dose reductions if needed and they’re not tolerating the medication.

Benjamin P. Levy, MD: One last question on T-DXd in breast cancer. I only ask this because I was covering the breast service about 3 months ago.… I was on the floor, this patient had leptomeningeal [LM] signs, and my colleagues said the patient needs T-DXd. And I thought that was from Crazy Town because these are large molecules that theoretically and biologically should not cross the blood-brain barrier. And we did it. And she had a miraculous turnaround in her LM disease. Have we seen this in the data, is that right? We’ve seen CNS [central nervous system] activity with these drugs, Kevin, and we’re starting to use it? And do you have an understanding of why this is happening with such a big drug? Does the blood-brain barrier not exist in breast cancer? Is it just that we don’t know if it’s in lung? I mean, how is it getting in and doing this?

Kevin Kalinsky, MD, MS: I’m going to mention 2 things. One, it’s important to know also that our TKI [tyrosine kinase inhibitor] that we have in breast cancer, HER2-targeted TKIs, can have good CNS penetration also. So even for a patient with LM, those are agents to think about also, but there are data in the context of CNS disease and these data have been published, for instance in Nature, where we see some CNS activity, and how I would rationalize it is just in terms of the payload, that some of that payload is being cleaved off. These are topoisomerase inhibitors we know can have some activity in the CNS. I think that’s what’s going on.

Benjamin P. Levy, MD: We’re not seeing this in lung [cancer] with the same drug. It has just not been observed; our TKIs go gangbusters in the CNS so it’s just an interesting phenomenon. It’s sort of akin to the KRAS G12C drugs working in KRAS G12C lung cancer but not KRAS G12C colon cancer. It’s one of these enigmas we’re trying to figure out. But I’m just interested in your experience with this.

Transcript is AI-generated and edited for clarity and readability.