Cardiovascular Risk and Menopausal Symptoms Associated With Oral SERDs

Ryan Haumschild, PharmD, MS, MBA: Let’s talk through the importance of the management of the adverse effects for SERDs [selective estrogen receptor degraders] and even the managed care decisions that come along with adverse effect management and real coverage criteria for these different treatments. It’s important that we continue to develop a plan to monitor patients on SERDs for adverse events, such as cardiovascular implications, bone loss implications, and menopausal considerations, and implement appropriate management strategies. Dr Vidula, how do oral SERDs impact bone health in patients who have ER [estrogen receptor]–positive and HER2 [human epidermal growth factor receptor 2]–negative metastatic breast cancer? Do we know enough to make a decision or a recommendation?

Neelima Vidula, MD: That’s a great question. There aren’t a lot of data in the literature that speak to how these oral SERDs impact bone health. In the EMERALD trial, they don’t report any bone-related events. That said, any agent that impacts the estrogen receptor—and a SERD does that—will theoretically have an impact on the bone because estrogen receptors are also present in the bone. In theory, it makes sense mechanistically that these oral SERDs could potentially decrease bone density. But many patients who have ER+/HER2- metastatic breast cancer present with or will develop bone metastases during their treatment because that’s a very common site of metastases for this disease. As a result, many of these patients, if they already have metastases, are usually getting a bisphosphonate every 3 months or so in clinic or getting a RANK ligand inhibitor such as denosumab to help prevent fractures and treat the bone metastatic disease. That provides some protection to the bones.

But if you had a patient who was on an oral SERD and did not have bone metastases, it wouldn’t be unreasonable to consider doing a bone-density scan, even though many of these patients are older to start with and postmenopausal. They may have had a bone-density scan in the recent past. If there’s evidence of osteoporosis or osteopenia, you could consider a bisphosphonate to help strengthen their bone health. If a patient is active and able to engage in weight-bearing exercise, take some vitamin D, and get some calcium in their diet, that can also help. Of course, you don’t want to overdo the calcium because patients with metastatic breast cancer sometimes can develop hypercalcemia.

Ryan Haumschild, PharmD, MS, MBA: It sounds as if it could be possible, but we want to wait till we see the data to drive more concrete decisions of supportive care. When we think about these supportive care considerations in treatment, Dr Lu, I want to turn to you because we talked about cardiovascular. What’s the potential impact on cardiovascular health for patients on oral SERDs in the treatment of ER+/ HER2- metastatic breast cancer?

Janice Lu, MD: There are 5 oral SERDs on the market being developed: 4 are in clinical trials, and 2 of those have cardiovascular effects such as bradycardia. However, for elacestrant, there are no indications of cardiovascular toxicity, such as QTC prolongation or bradycardia. If you talk about hyperlipidemia, it exists. Less than 2% of patients had grade 3/4 hyperlipidemia toxicity in the EMERALD trial, and most patients had grade 1/2. When I see my patients, I share with them that this is a potential adverse effect. I want to check your lipid profile as a baseline, and I want to check it periodically due to treatment, while you’re taking elacestrant. The correlation between hyperlipidemia and cardiovascular toxicity is remote but somehow linked. This is 1 factor: the adverse effect that leads to that.

Ryan Haumschild, PharmD, MS, MBA: It’s important to manage as we look at population health as a whole and at patients in our plan. There are a lot of patients with comorbidities, and they might have metabolic syndrome. They might have existing cardiovascular disease. [We need to] be thoughtful as we tee up these different therapies, making sure we’re having that discussion for the patient, considering some of their unique characteristics.

When we talk about different impacts, Dr Vidula, we also want to think about the risk of menopausal symptoms in our patients because that impacts quality of life, and that’s something you’re always keeping an eye on. How does the risk of menopausal symptoms differ between oral SERDs and other endocrine therapies for these patients?

Neelima Vidula, MD: Unfortunately, many endocrine therapies are associated with vasomotor symptoms, and oral SERDs are also associated with that. In the EMERALD study, hot flashes were 1 of the more common adverse effects experienced by patients. That’s not too dissimilar from what we see with aromatase inhibitors, where hot flashes are a known adverse effect. It’s something to be aware of. This is triggered by changes in the serum estrogen level in patients, so that’s what causes them. But that’s definitely something we can manage. If patients tell us they’re having hot flashes, there are medications that can be used to mitigate that adverse effect. Counseling patients about it is important. In addition, myalgias were also seen in the EMERALD study with elacestrant, so that’s something to be mindful of as well. With aromatase inhibitors, which have been on the market for a lot longer, we can see arthralgias often. It’s not too dissimilar, but it’s important to educate patients that they may have muscle achiness and joint pain, [so you can] manage that. Sometimes you can use a nonsteroidal anti-inflammatory agent to help with symptoms.

Transcript edited for clarity.