Real-world data presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) indicates that elacestrant, an oral selective estrogen receptor degrader (SERD), provides similar or slightly improved outcomes in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer with ESR1 mutations, compared to results from the phase 3 EMERALD trial. The analysis offers insights into the drug's effectiveness in a broader patient population, including those treated beyond the second line of therapy.
Elacestrant's Performance in Real-World Settings
The real-world analysis included 742 eligible patients with a mean age of 63 years. The median real-world time to next treatment (rwTTNT) was 6.43 months (95% CI, 5.60-8.03), and the median real-world time to treatment discontinuation (rwTTD) was 4.6 months (95% CI, 4.03-5.40). These figures are in line with, or slightly higher than, the progression-free survival (PFS) of 3.8 months observed in the EMERALD trial, which compared elacestrant to standard-of-care endocrine therapy.
The EMERALD trial's findings, published in Clinical Cancer Research, demonstrated a statistically significant improvement in PFS with elacestrant compared to standard endocrine therapy in patients with ESR1-mutated advanced breast cancer. Elacestrant received FDA approval in January 2023 for postmenopausal women, and adult men, with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
Impact of Treatment Line and PIK3CA Alterations
The real-world analysis also revealed that the line of treatment did not significantly impact outcomes. For second-line elacestrant, rwTTNT was 8.8 months, and rwTTD was 5.3 months. In the third-line setting, rwTTNT was 5.9 months, and rwTTD was 4.5 months. For fourth-line or later, rwTTNT was 6.4 months, and rwTTD was 4.6 months. This suggests that elacestrant maintains its activity even in heavily pre-treated patients.
However, patients with alterations in the PIK3CA pathway experienced worse outcomes. Specifically, these patients had a shorter time to next treatment (5.2 vs. 8 months), shorter time to treatment discontinuation (4 vs. 5.3 months), and worse overall survival. According to Dr. Rinath Jeselsohn, Dana-Farber Cancer Institute, this underscores the need for precision medicine and combination treatments in specific patient subgroups.
Patient Characteristics and Prior Treatments
The study population had diverse prior treatments, including aromatase inhibitors (90%), fulvestrant (53%), CDK4/6 inhibitors (83%), chemotherapy (41%), alpelisib (10%), trastuzumab deruxtecan (8%), and sacituzumab govitecan (4%). The most common sites of metastasis were bone (73%), liver (31%), and lung (15%).
Implications for Clinical Practice
"A real-world analysis of patients with advanced hormone receptor-positive breast cancer with ESR1 mutations identified more than 700 patients treated with elacestrant since the approval with very specific criteria," Dr. Jeselsohn concluded. "The time to treatment discontinuation and time to next treatment were overall in the range are slightly higher compared to PFS seen in the EMERALD trial, and most of the patients received [elacestrant] beyond second line of treatment for metastatic disease."
