New endocrine therapy options for patients with breast cancer on the horizon, expert says
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Endocrine therapies have revolutionized the field of breast cancer, with significant improvements in survival outcomes among patients with hormone receptor-positive disease.
“Endocrine therapy is the mainstay of treatment for patients with localized and metastatic hormone-receptor-positive breast cancer,” Aditya Bardia, MD, MPH, director of the breast cancer research at Mass General Cancer Center and associate professor at Harvard Medical School, said during an interview with Healio. “Patients with localized hormone-receptor-positive breast cancer usually undergo treatment with endocrine therapy in the adjuvant setting, and for those with metastatic disease, the recommended first-line treatment is endocrine therapy along with a cyclin-dependent kinase [CDK] 4/6 inhibitor.”
There are two classes of endocrine therapies, including selective estrogen receptor modulators and aromatase inhibitors.
“The selective estrogen receptor modulators, such as tamoxifen, are predominantly used for patients with premenopausal localized breast cancer,” Bardia said. “Whereas the other class of medications, aromatase inhibitors, including letrozole, exemestane and anastrozole, are generally recommended as first-line for patients with postmenopausal localized ER-positive breast cancer in the adjuvant setting. Then there is a third option for patients with metastatic disease, fulvestrant, but is given as an intramuscular shot which can be inconvenient for patients.”
There is a need for new targeted agents, according to Bardia.
“Clinically, there has been a need for better endocrine agents, particularly oral options and similar to fulvestrant, but stronger and better,” Bardia said. “From a clinical development perspective, there’s been a lot of interest in oral versions of selective estrogen receptor degraders, because that could replace fulvestrant to have an oral option for patients, and this has led to clinical development of multiple novel endocrine agents, such as elacestrant, giredestrant, camizestrant, imlunestrant, ARV471, among others.” Bardia also cautioned that these novel therapies are not yet approved for breast cancer and cannot be recommended outside of a clinical trial at this time.”
EMERALD trial
Results of the randomized phase 3 EMERALD trial showed improvements in PFS with the novel, oral selective estrogen receptor degrader, elacestrant, compared with standard-of-care endocrine therapy among a cohort of patients with estrogen receptor-positive, HER2-negative metastatic breast cancer.
Bardia and colleagues enrolled 477 patients who were previously treated with one to two lines of endocrine therapy (43.3% received two prior endocrine therapies), who also required a neoadjuvant CDK4/6 inhibitor and up to one line of chemotherapy.
Researchers assigned patients to either 400 mg daily elacestrant (n = 239) or standard-of-care endocrine monotherapy (n = 238). PFS served as the primary endpoint among all patients and separately among those with detectable ESR1 mutations (47.8%).
Results showed improvements in PFS among all patients (HR = 0.7; 95% CI, 0.55-0.88) and among the subset of patients with ESR1 mutations (HR = 0.55; 95% CI, 0.39-0.77).
“The company has now filed for regulatory approval based on these findings,” Bardia said. “Overall, elacestrant demonstrated scientific proof of monotherapy efficacy, compared to other endocrine agents, for patients with metastatic ER-positive breast cancer. In terms of toxicity, elacestrant was generally well-tolerated, with nausea being the most common side effect. Of note, the rate of treatment discontinuation was low.”
Barriers in access
Despite the various endocrine therapy options available, barriers in access to the treatment remain, according to Bardia.
“For one, because fulvestrant has to be given as an intramuscular shot, there may be patients who cannot travel to a clinician’s office for visits,” Bardia said. “For example, during the COVID-19 pandemic, this was a real problem in terms of coming into the clinic or the hospital for injections. For some patients, that could be a barrier as opposed to just an oral agent that they can take at home.”
The second barrier is the potential for side effects.
“Aromatase inhibitors tend to cause musculoskeletal symptoms and bone loss, whereas tamoxifen can cause blood clots, hot flashes and weight gain,” Bardia said. “There are some patients who would discontinue these treatments because of the side effects, which leads to low adherence and does impact outcomes. Because of these barriers, there is a great need to develop alternate endocrine therapies so that patients have additional treatment options.”
Looking ahead
Looking ahead, Bardia said there are unmet needs with endocrine therapy for breast cancer.
“The first need is to have even better endocrine agents to give patients more options,” he said. “Second, strategies are needed to improve adherence and ensure that patients can derive maximum benefit from these endocrine therapies. Third, we need to better understand resistance to endocrine therapies.”
Certain patients may have disease recurrence despite adjuvant therapy, he continued.
“After a while, patients in the metastatic setting may experience disease progression on endocrine-based therapy,” Bardia said. “If we understand mechanisms governing endocrine resistance, we can address them and improve outcomes for our patients.”
“This can continue to be achieved through various treatment strategies in terms of protection, management novel therapies and coming up with better treatment strategies,” he said. “Our overarching goal is for patients to live longer and have improvement in their quality of life, i.e live well.”
Reference:
Bidard FC, et al. J Clin Oncol. 2022;doi:10.1200/JCO.22.00338.
For more information:
Aditya Bardia, MD, MPH, can be reached at bardia.aditya@mgh.harvard.edu.
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