Ensuring Optimal Clinical Benefit From Oral SERD Therapy in Patients With HR+/HER2- Breast Cancer

The ongoing research in oral selective estrogen receptor degrader (SERD) therapy represents exciting developments in the management of hormone receptor (HR)–positive/HER2-negative metastatic breast cancer. With the recent FDA approval of elacestrant, an oral SERD, there is an alternative to the injectable SERD, fulvestrant.

Several clinical trials are ongoing evaluating other oral SERDs (eg, amcenestrant, camizestrant, giredestrant, and imlunestrant), but in this commentary I will focus on tips to mitigate and manage the most common adverse events (AEs) associated with elacestrant.

Elacestrant AEs

The most common AEs of elacestrant are nausea, musculoskeletal pain, fatigue, elevated cholesterol/triglycerides, and changes in liver enzymes. However, the 3 AEs that most impact quality of life and adherence to therapy are nausea, musculoskeletal pain, and fatigue. In order to ensure medication adherence, healthcare professionals should be aware of approaches to mitigate and manage these AEs. Here I discuss approach.

Nausea

For nausea, I recommend taking elacestrant with food. This recommendation tends to work very well for patients, but if they continue to experience nausea and/or vomiting, I prescribe antiemetics as needed. I advise patients to take an antiemetic 30 minutes prior to the dose while still instructing them to take their dose with food.

Other potential interventions to mitigate nausea include:

• Drink plenty of water
• Avoid heavy or spicy foods
• Eat smaller meals more frequently throughout the day
• Take elacestrant at night

Musculoskeletal Pain

In the phase III EMERALD study, the rates of musculoskeletal?pain were very similar across the standard of care and elacestrant treatment arms.

When managing musculoskeletal pain for oral SERDs, I employ the same strategies as I do for standard of care endocrine therapies (eg, aromatase inhibitors, fulvestrant). These strategies include:

• Daily exercise
• Gentle stretching
• Acupuncture
• Use of analgesics?(eg, nonsteroidal anti-inflammatory drugs, acetaminophen) before exercise or as needed

Fatigue

For patients experiencing fatigue, I recommend daily movement and exercise, maintaining a balanced diet, and optimizing sleep habits. I encourage patients to set realistic priorities and expectations, and to pace themselves throughout the day. Since fatigue is often multifactorial, I evaluate for changes in mood that may be contributing to tiredness from therapy.?

Elacestrant dose reductions may be necessary if quality of life is significantly impacted despite conservative measures.?

Laboratory Abnormalities

To monitor for laboratory abnormalities—notably?hypercholesterolemia and elevated triglycerides—I obtain a baseline lipid panel prior to initiating elacestrant, then at least every 3 months. Depending on the patient’s risk, I may check their lipid panel more frequently. Working closely with the patient’s primary care physician may be needed to optimize lipid control before and during therapy. I also encourage patients to follow a low cholesterol?diet and will refer them to nutritionists or dietitians if needed.?

In addition to monitoring the patient’s lipid panel, I follow chemistry panels that include liver function test monitoring (eg, complete metabolic panel) at baseline and every 3 months while on elacestrant. Dose reductions are recommended in the setting of moderate liver impairment.

Lastly, it is important to review the patient’s medication list for other medications that affect liver enzymes, particularly medications that inhibit or induce the CYP3A4 pathways, as these may impair therapeutic concentrations of elacestrant.

Patient Education

An advantage of oral SERDs is the increased flexibility for patients to take their medication at home as they are not required to come to the office for treatment each month. However, less frequent contact with the office may result in missed opportunities for assessment of AEs and adherence to therapy.

I find that it is key to educate patients regarding expected AEs prior to starting treatment and discuss strategies to promote adherence, to fully optimize patient outcomes and improve quality of life. I also review the data that led to the approval of elacestrant in layman’s terms, so patients understand the importance of taking their treatment as prescribed.?

Improving Adherence

To promote adherence to oral therapy, I suggest to my patients that they establish a routine and take their medicine at the same time or with the same meal every day. Using a pill box or smartphone app may be helpful for individuals to stay consistent with daily dosing. Likewise, keeping the prescription bottle in a location in the home in which the patient spends considerable time (eg, kitchen, bathroom, nightstand) may also serve as a visual reminder.

For patients with moderate to severe treatment-related AEs, I find it helpful to schedule an interval telehealth visit (either phone or video) to evaluate and adjust the supportive plan as needed without causing too much inconvenience in the patient’s daily routine.

In all, patients may experience significant AEs related to therapy that may affect their adherence to a daily dosing schedule. It is important for healthcare professionals to evaluate patients for AEs at every follow-up visit. In addition, patients should be instructed to call the clinic with any new or worsening symptoms—no matter how big or small.

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Your Thoughts?

What strategies have you found most helpful to promote adherence and manage treatment-related AEs in your patients receiving oral breast cancer therapy? Leave a comment to join the discussion.