Katherine C. Ansley, MD, is an associate professor in the Section of Hematology and Oncology in the Department of Internal Medicine at Wake Forest University School of Medicine and a breast cancer leader at Atrium Health Wake Forest Baptist Hematology and Oncology - Cancer Center.

Katherine C. Ansley, MD, highlights the role of elacestrant in treating ER-positive, HER2-negative, ESR1-mutant, advanced breast cancer with metastases.

Dr Ansley on the Role of Elacestrant in ER+, HER2– Advanced Breast Cancer

“One of the best things about elacestrant is how well it is tolerated. We didn’t see as many [adverse] effects because it is a more endocrine-based therapy. One thing we’re always looking for are drugs that work better with fewer AEs, and we are seeing that with these [treatments].”

Katherine C. Ansley, MD, a breast medical oncologist at the Atrium Health Wake Forest Baptist Hematology and Oncology – Cancer Center and an associate professor of cancer medicine at the Wake Forest University School of Medicine, highlighted the role of the oral selective estrogen receptor degrader (SERD) elacestrant (Oserdu) for the treatment of patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer who previously received 1 or 2 lines of therapy with a CDK4/6 inhibitor plus fulvestrant (Faslodex) or an aromatase inhibitor.

 for the treatment of patients with ER-positive, HER2-negative, 

-mutated advanced or metastatic breast cancer with disease progression after at least 1 line of endocrine therapy.

Based on findings from subgroup analyses of the phase 3 EMERALD trial (NCT03778931), there was some initial concern about using elacestrant in patients with bone, liver, or lung metastases, Ansley began. However, significant responses were observed among patients with liver and/or lung metastases who were treated with elacestrant, she explained. Specifically, in those with liver and/or lung metastases and 

-mutant disease, the median progression-free survival (PFS) was 7.3 months and 1.9 months with elacestrant vs standard of care (SOC), respectively (HR, 0.35; 95% CI, 0.21-0.59), she added. Furthermore, patients with bone metastases experienced a median PFS of 9.1 months with elacestrant compared with 1.9 months with SOC (HR, 0.38; 95% CI, 0.23-0.62), which is encouraging, according to Ansley.

Beyond the median PFS, Ansley also noted that elacestrant was well tolerated, with minimal adverse effects (AEs) observed because it is an endocrine-based therapy. Of note, the majority of AEs observed were grade 1/2 in the overall patient population. Treatment discontinuations due to any treatment-related AE occurred in 8 patients treated with elacestrant (n = 237) vs 2 treated with SOC (n = 230). No treatment-related deaths were reported in either arm. Additionally, the updated safety analysis revealed that the most common any-grade gastrointestinal AEs observed included nausea (elacestrant, 35%; SOC, 19%) and vomiting (19%; 9%).

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"The phase 3 INAVO120 trial was an interesting study for patients who seemed to have very high-risk disease. It was actually a first-line study right now. Prior to this, we'd only been using PIK3CA inhibitors in the second line, but this study [involved] patients who had progressed during or within 12 months of stopping their adjuvant endocrine therapy."

Katherine C. Ansley, MD, an associate professor in the Section of Hematology and Oncology in the Department of Internal Medicine at Wake Forest University School of Medicine and a breast cancer leader at Atrium Health Wake Forest Baptist Hematology and Oncology - Cancer Center, discussed findings from the phase 3 INAVO120 trial (NCT04191499), which evaluated the addition of inavolisib (Itovebi) to palbociclib (Ibrance) and fulvestrant (Faslodex) in the first-line treatment of patients with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)–positive, HER2-negative advanced breast cancer.

Ansley noted that INAVO120 addressed a particularly high-risk population: patients whose disease recurred either during adjuvant endocrine therapy or within 12 months of completing it. Prior to this study, PIK3CA inhibitors had only been used in later-line settings. However, this trial moved the use of inavolisib into the first-line setting, reflecting a significant shift in treatment strategy for patients with aggressive disease biology.

Updated findings demonstrated a clinically meaningful improvement in progression-free survival (PFS) with the triplet combination. Patients who received inavolisib plus palbociclib and fulvestrant experienced a median PFS of 15.0 months (95% CI, 11.3-20.5), compared with 7.3 months (95% CI, 5.6-9.3) for those who received palbociclib and fulvestrant alone. The hazard ratio for disease progression or death was 0.43 (95% CI, 0.32-0.59; P < .0001), representing a 57% reduction in risk with the triplet regimen, Ansley explained.

These results supported the October 2024 FDA 

approval of inavolisib (Itovebi) paired with palbociclib (Ibrance) and fulvestrant (Faslodex)

 as a treatment for adult patients with endocrine-resistant, 

-mutated, hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer after recurrence on or following completion of adjuvant endocrine therapy. Ansley concluded by emphasizing the significance of the approval, given the high-risk nature of this patient subset and the demonstrated efficacy of the targeted approach.

Katherine C. Ansley, MD, discusses the importance of the phase 3 INAVO120 trial in PIK3CA-mutated, hormone receptor–positive, HER2-negative breast cancer.

Katherine C. Ansley, MD

Articles

Dr Ansley on the Role of Elacestrant in ER+/HER2– Advanced Breast Cancer

Dr Ansley on Inavolisib Plus Palbociclib/Fulvestrant in PIK3CA-Mutated HR+/HER2– Breast Cancer