Antibody-Drug Conjugates in Breast Cancer: Strategies for Toxicity Management - Episode 8
Strategies that can be used to mitigate and manage adverse events associated with sacituzumab govitecan therapy for triple-negative breast cancer.
Kevin Kalinsky, MD, MS: Kandra, in clinic, how have patients tolerated the therapy? Talk us through some of the toxicities you’ve seen with some of these patients.
Kandra Horne, DNP, MSN, WHNP-BC: For the most part, our patients have been tolerating this treatment pretty well. If you look at the ones who’ve been treated, they’ve been heavily pretreated. Some of those patients have neutropenia. You’ve probably seen the counts affected from previous treatments, fatigue, and what it looks like to be a patient with metastatic breast cancer. We see this sooner than later. Even though we initially start with day 1 and day 8, there are times where we’ve been able to switch the schedule to day 1 and day 15 to protect the counts. Sometimes we add something like Neulasta [pegfilgrastim] to support their counts. But that’s because these patients were heavily pretreated. There’s been fatigue and some nausea, but more commonly fatigue and neutropenia have been the adverse effects that we mostly see with these patients.
Kevin Kalinsky, MD, MS: In all the patients I’ve treated with this agent, everybody lost their hair. Have any of you treated somebody who’s not had alopecia with this?
Allison Butts, PharmD, BCOP: I had a patient.
Kandra Horne, DNP, MSN, WHNP-BC: I have.
Kevin Kalinsky, MD, MS: Allison, are there any other strategies for mitigating some of these toxicities? Kandra mentioned the fatigue, and certainly that’s something we see in clinic, and growth factor support is sometimes needed. Have you seen any other issues, such as significant gastrointestinal issues, where you needed to escalate beyond oral medications?
Allison Butts, PharmD, BCOP: Not escalating beyond oral medications, but it’s important to consider the pharmacology: the cytotoxic payload of sacituzumab is SN38. If you figure you’re giving the active metabolite of irinotecan, it’s not surprising that GI [gastrointestinal] toxicities will come into play. In my experience, it’s been cycle by cycle, honestly. We haven’t seen consistent diarrhea. It will flare up 1 cycle and not be too much of an issue the next. Fortunately, we’ve been able to manage that with oral medications.
The other adverse effect I want to mention that hasn’t been talked about is infusion reactions with this agent. With this drug, the first dose has to be given over a 3-hour period. Subsequently that could be 1 to 2 hours. It’s recommended that we premedicate with antihistamines, antipyretic, and corticosteroids to try to limit that effect. Fortunately with those premedications, I haven’t seen any infusion reaction. It seems to be doing well, but that’s a consideration in terms of scheduling, patient acceptance, etc.
Kevin Kalinsky, MD, MS: Kandra raises a good point: these are adverse effects that we see in a heavily pretreated population as this drug moves up. We’ll see whether the grade of fatigue is the same. Allison, when you were talking about premedications, for the antiemetics commonly utilized, do you find that most are using IV [intravenous] antiemetics and then de-escalating if patients aren’t having any nausea? Institutionally, how are things commonly practiced?
Allison Butts, PharmD, BCOP: Most institutions that I’m aware of are using oral antiemetics and treating it as a moderate medical potential drug, which is appropriate. Fortunately, we haven’t seen a lot of nausea. Our GI toxicities have been more diarrhea related, and the premedications we’ve been using have been successful.
Kevin Kalinsky, MD, MS: Komal, how do you start with antiemetics?
Komal Jhaveri, MD, FACP: My experience has been a little like Allison’s. Sometimes I’ve seen the hypersensitivity reactions. We obviously follow the 3 hours, but you’ll very rarely still see a patient struggle, and you’ll have to optimize the Benadryl [diphenhydramine] and the steroid as premedications during infusions. Diarrhea is something I’ve seen often, plus a lot of alopecia. For nausea, as I said, for patients who struggle more with nausea, we’ve been giving palonosetron during the infusion; otherwise, they’ve been getting ondansetron as needed every 8 hours. But for the diarrhea and the neutropenia…sometimes we’ll have to do dose reductions even if there’s struggle. But neutropenia, diarrhea, and alopecia are the top 3 adverse effects.
Kevin Kalinsky, MD, MS: Kandra, any other clinical pearls about this agent before we move on?
Kandra Horne, DNP, MSN, WHNP-BC: No. Looking at the patient from where they are and the indication when they’re coming in, you’ve raised a great point in stating that as the indication has changed, where might this medication be at a further line, such as second line or later on with the heavily pretreated patients. That might make a difference in regard to some of the toxicities they’ve been experiencing.
Kevin Kalinsky, MD, MS: I agree. This agent is being evaluated in the operable setting, and we a have study that’s combining this with immunotherapy. Komal had mentioned that we’ll see whether the randomized phase 3 trial leads to an approval of patients with hormone receptor–positive vs negative disease, because the phase 1/2 basket studies show the same efficacy in that population compared with triple-negative [breast cancer]. Hopefully, we’ll see some of those data [soon].
Transcript edited for clarity.