Managing Adverse Events for Patients With Breast Cancer
Heather Moore, CPP, PharmD, Duke Cancer Center, Durham, North Carolina, discusses the management of adverse events for patients with breast cancer.
Dr Moore highlights the identification and treatment of toxicities associated with CDK/6 inhibitors, hyperglycemia with PI3K/AKT inhibitors, and interstitial lung disease (ILD) with trastuzumab deruxtecan (T-Dxd).
Transcript:
Hello, my name is Heather Moore. I'm a clinical oncology pharmacist at the Duke Cancer Institute. I'm here today at Great Debates [in Solid Tumors]. If you weren't able to make it for today, in general, we looked at toxicities for breast cancer therapies in hormone receptor-positive, HER2-negative treatments.
That encompassed CDK4/6 inhibitors. We've been using CDK4/6 inhibitors for almost a decade now, but now we have them in the adjuvant space. This piece was focused on abemaciclib and ribociclib, based off of the monarchE and NATALEE trials. This looked at the inclusion criteria for those studies, as well as the toxicities associated. Focusing on abemaciclib-induced diarrhea management strategies, utilizing loperamide, but also the dose-escalation strategies. This was recently presented at ASCO, based off of the TRADE study. The best ways of how to incorporate that into clinical practice.
With a focus on ribociclib, also thinking about drug interactions since it is a CYP3A4 substrate, but also that it's a CYP3A4 inhibitor, and we do have to be mindful of QT prolongation, so also thinking about pharmacodynamic interactions, being mindful of anxiolytics, pain medications, CINV [chemotherapy-induced nausea and vomiting] medications, therapies that we can be mindful of when we're choosing from a supportive care aspect to ensure that we're reducing the risk of QT prolongation.
Then we've shifted into a newer class of agents, PI3K inhibitors, as well as a AKT inhibitors, so that's our alpelisib, inavolisib, and then capivasertib, going through how we're using these agents: dosing, but really focusing on the hyperglycemia piece, focusing on CTCAE grading criteria, how that may vary between SOLAR-1 and BYLieve compared to CAPItello-291, and then the INAVO-120 study in terms of how hyperglycemia was categorized. And that makes a difference because sometimes that can represent hyperglycemia in some of those latter trials.
Also focusing on how do we monitor, how do we manage, focusing a little bit on mitigation strategies in terms of prophylaxis with metformin, how we extrapolate from the METALLICA data so that we can identify high risk patients and start them on anti-hyperglycemic agents before they're starting therapy to help reduce the risk of hyperglycemia. For patients that develop hyperglycemia while on these therapies, really important to focus on the mechanism of the anti-hyperglycemic that we're using. Being mindful that we want insulin sensitizers, not agents are going to increase insulin release because that can reactivate that PI3K pathway. So really using metformin as our standard. Also, considering SGLT2 inhibitors, we have a lot of emerging data and then also TZD therapies really noting that it's an important to identify the best medications for management.
And then finally, trastuzumab deruxtecan-induced ILD. This is an agent that is really taking over solid tumors, anyone with a HER2-positive tumor now, based off the pan-indication, can use this agent. And we've been using it in the breast cancer space for over 5 years now. But being mindful of what are risk factors that may put someone at a higher risk of ILD, noting for patients that develop ILD, really differentiating between what is a grade 1, a grade 2, grade 3, and so on, and why that's important, how we monitor these patients throughout treatment with T-Dxd, knowing that steroids are our mainstay of treatment, but also that for patients that they develop a grade 1 ILD, we can successfully retreat them and know that it's very unlikely that ILD does recur, and if it does, it is at a much lower grade, grade 1 or 2 event. That does help us, encourage us in the clinical space that we can treat these patients with this drug and continue therapy.
