ADCs in the Treatment of Breast Cancer and Gastric Cancer and Managing AEs Associated with ADCs - Episode 2
Contextualizing the use of T-DXd in breast cancer and gastric cancers respectively, panelists highlight optimal management of adverse events in these settings.
Sarah Donahue, MPH, NP, AOCNP: The combination of trastuzumab, pertuzumab, and docetaxel is the well-established frontline setting for patients with metastatic HER2-positive breast cancer. The first-line study that showed this was efficacious treatment was CLEOPATRA, so, I suppose we use this regimen in pretty much all of our patients. There are some patients who may have received the docetaxel portion with their early stage disease, with the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. If they had a metastatic recurrence within 6 months, you may be choosing a different line of therapy at this point, but generally, if it’s been greater than 6 months, definitely if it’s been greater than a year, you’d be choosing this as your first-line therapy for these patients.
The way it’s given is for 6 to 8 cycles often, then get scans, and if it shows improvement of their disease, you can stop the chemotherapy and continue with the antibodies alone and add an aromatase inhibitor or something like that if they are hormone positive. If not, you continue the antibodies alone, then follow them with scans. That’s exactly what happened with this patient here. After progression on this first-line therapy, historically, the next line of therapy would be T-DM1, or trastuzumab emtansine, which was shown in the EMILIA trial. But more recently, trastuzumab deruxtecan [T-DXd] has been approved in this setting, and it was shown in the DESTINY-Breast03 trial to be superior to trastuzumab emtansine. So, newly now, we are giving the trastuzumab deruxtecan as your next line of therapy.
The common adverse event associated with trastuzumab deruxtecan for patients with breast cancer is nausea. We have a lot of nausea, so we give them a lot of premedications; we include the aprepitant-type premedication along with a long-acting 5-HT3 inhibitor. I give dexamethasone as a premedication, and I also make sure that they have taken home medications such as odansetron, lorazepam, and prochlorperazine. Sometimes I’m adding olanzapine for patients who are having a lot of nausea, and often omeprazole or something similar for the acid reflux that happens. I’m not seeing as much diarrhea as they may have seen in the trials, but we are making sure they have Imodium on hand at home.
The main adverse effect is nausea. I have patients with fatigue. The hair loss is minimal, although I have had 1 in 10 patients lose a lot of hair, with patchy loss of hair, so it’s not 100% that it’s just going to be hair thinning. Then finally we have interstitial lung disease [ILD] or pneumonitis that can occur, which I’m not seeing that often. This case study does exhibit a patient who did experience that, but because they’re metastatic, they are getting CT scans all the time. So, we’re luckily finding asymptomatic ILD and pneumonitis, and we are able to treat them appropriately with prednisone early.
Are people in the gastric cancer world experiencing different adverse effects with their patients, or is it similar?
Theresa Wicklin Gillespie, PhD, MA, RN, FAAN: I can address that. Looking at both practical experience but particularly the data from the trials that we’ve had—which admittedly the number of patients on the first 2 published gastric trials has been fairly small—you do see interstitial lung disease as well as pneumonitis. But I think the thing that is more profound and of concern is neutropenia. You also see common adverse effects as you mentioned for breast cancer, such as nausea, vomiting, fatigue, things like that. In the DESTINY-Gastric01 trial, the rates of neutropenia were about 72%, with a considerable number having grade 3 or 4, and there was about a 5% rate of febrile neutropenia. So those are areas we would definitely want to focus on.
Jamie Carroll, APRN, CNP, MSN: I think the dose is a little different in gastric cancer vs breast cancer. That could be the reason why you are noticing a bit more neutropenia. I’ve seen neutropenia but not febrile neutropenia with trastuzumab deruxtecan. What is your experience with increased AST [aspartate aminotransferase] and ALT [alanine transaminase]? I find that we’re having to closely monitor and hold or dose reduce based on their increase in liver enzymes.
Sarah Donahue, MPH, NP, AOCNP: I have not had increased liver enzymes in any of my patients I can think of to date. Has anybody else? That’s been happening in several of your patients?
Jamie Carroll, APRN, CNP, MSN: Yes, I see it frequently, 6.4 versus 5.4 measurements.
Sarah Donahue, MPH, NP, AOCNP: Are you seeing with the gastric cancers that you’re having to give them pegfilgrastim right off the bat, or are you seeing how they do, and then adding in filgrastim, like the short-acting daily dosing, as needed? Sorry, I’m switching back to neutropenia.
Elizabeth Prechtel Dunphy, DNP, CRNP, AOCN: In our practice, we don’t do that prophylactically. We would monitor the patient during the course of therapy, and if it were to occur, we would delay treatment and then consider a dose reduction before adding the growth factor support. At least that’s what our practice is at this time.
Sarah Donahue, MPH, NP, AOCNP: Are there any other adverse events? Are you seeing hair loss like I’m seeing, where about 1 in 10 are losing quite a bit of hair? I don’t often offer patients the cold capping systems we have here. I don’t know what you have at your institutions, but we don’t offer that to them as of now. But I’ve definitely started thinking that maybe we should.
I’ve also had a few patients who have had some thrombocytopenia, just 1 or 2. Are you seeing that in the gastric cancer dosing at all, or is it mostly neutropenia?
Theresa Wicklin Gillespie, PhD, MA, RN, FAAN: I would say neutropenia is more prevalent, but I’d say myelosuppression across the board, including anemia. So, it hits all the bases.
Jamie Carroll, APRN, CNP, MSN: I think it was reassuring to know that the updated safety profile did not show prolonged adverse effects, and in fact GI [gastrointestinal] adverse effects are decreased over time, in addition to the alopecia improvements.
Transcript edited for clarity.