Virginia Kaklamani, MD: Now, regarding adverse events, Elizabeth, when we examine patients with positive HER2 (human epidermal growth factor receptor 2) negative metastatic disease, how do we typically manage these adverse events in terms of treatment? And how do we select treatments based on these adverse events?

Elizabeth Diaz, PA-C: In these most at-risk cancer patients, it's crucial to inform them upfront that it's not a curable disease. Our primary goal is to extend their lives, ensuring their quality of life remains high. Many have young children, making it a paramount concern. The patient's history often dictates our approach. We've discussed several agents and supportive measures. To recap: as you mentioned, there's less than a 1% risk of severe infection from neutropenia caused by CDK4/6 (Cyclin-Dependent Kinases 4 and 6) inhibitors. We usually don't stop treatment unless a fever or infection manifests. Maintaining them on these drugs is essential. However, dose reductions can sometimes improve their quality of life without impacting overall survival. For Ribociclib, there's a concern about liver dysfunction and QTc prolongation. Although rare, we monitor with EKGs (Electrocardiograms) at baseline and during the treatment. Ensuring they're not on other QTc-prolonging agents is also essential. For example, if a patient's depression or anxiety is well-controlled on a medication like Citalopram or another SSRI (Selective Serotonin Reuptake Inhibitor), which might increase their risk of QTc prolongation, another CDK4/6 inhibitor might be preferable. A clinical pharmacist's involvement is invaluable here, especially when considering other drugs like fluoroquinolones or appetite stimulants like Mirtazapine.

We discussed managing diarrhea associated with certain treatments. Having Loperamide on hand and a clear plan for its use is essential. Early follow-ups can help manage these adverse events. Pneumonitis with the two drugs we discussed earlier is also a concern.

Virginia Kaklamani, MD: Let me touch on the importance of the clinical pharmacist's role and frequent follow-ups for patients on oral agents. Adherence is vital. A quick follow-up, even just a phone call within a week of starting a new medication, is crucial. It's alarming how often patients might discontinue their medication without informing us. Another recent finding from clinical trial data indicates that patients on proton pump inhibitors (PPIs) have decreased progression-free survival with CDK4/6 inhibitors. PPIs seem to reduce drug absorption, thus affecting efficacy. So, discussing chemotherapy, how do you guide patients through their options?

Elizabeth Diaz, PA-C: Although oral, some agents, like capecitabine, can be challenging due to side effects. Before the advent of CDK4/6 inhibitors, capecitabine was effective but caused issues like hand-foot syndrome. Comparatively, drugs like everolimus might be better tolerated but require frequent visits. Neuropathy also factors in when considering a return to taxanes.

Virginia Kaklamani, MD: It's crucial for patients to understand the potential toxicity of oral chemotherapies. There's a misconception that oral agents are less potent, which is far from the truth. The potential for alopecia also influences our treatment choices. How do you discuss the potential adverse events from drugs like sacituzumab govitecan and trastuzumab deruxtecan?

Elizabeth Diaz, PA-C: Informing patients of the risk of severe pneumonitis is paramount. While many of us are familiar with immunotherapy, the pneumonitis associated with these drugs can be even more aggressive. Early signs like a cough or shortness of breath require immediate attention. Nausea and vomiting are also concerns, necessitating aggressive management strategies. With sacituzumab govitecan, diarrhea and hair loss can be side effects, but its efficacy often outweighs these concerns.

Virginia Kaklamani, MD: I concur. The efficacy data for these medications, showing improvement in disease-free and overall survival compared to single-agent chemotherapy, is truly impressive.