Vaginal/Vulvar Symptoms Show Improvement With Lasofoxifene in Postmenopausal Women With ER+/HER2–, ESR1-Mutated Breast Cancer

Shari B. Goldfarb, MD

A small secondary analysis of the phase 2 ELAINE-1 trial (NCT03781063) suggests that lasoxifene may be associated with a better improvement in vaginal/vulvar symptoms than fulvestrant (Faslodex) in premenopausal patients with locally advanced or metastatic estrogen receptor (ER)–positive/HER2-negative breast cancer harboring an ESR1 mutation.¹

The findings, which were shared as part of a poster presentation delivered during the 2023 International Society for the Study of Women’s Sexual Health Annual Meeting, indicated that among those who completed the vaginal (VAS) and vulvar (VuAS) assessment scales, the mean composite VAS/VuAS score decreased by 76% from baseline to week 16 in those who received lasofoxifene vs 36% for those given fulvestrant.

In the group of patients who had at least 1 moderate or severe symptom at baseline, lasofoxifene again resulted in a greater reduction in mean composite VAS/VuAS score from baseline to week 16 than fulvestrant, at 72% and 32%, respectively. Moreover, the mean score for the most bothersome symptom decreased by 65% from baseline to week 16 in the investigative arm vs only 5% in the control arm.

“This small-sample-sized exploratory analysis shows that lasofoxifene at 5 mg/day may potentially provide clinical benefits on vaginal and sexual health when treating metastatic breast cancer,” Shari B. Goldfarb, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center in New York, New York, stated in a press release.

Patients with ESR1-mutated, ER-positive/HER2-negative metastatic breast cancer who progressed on previous aromatase inhibitors plus a CDK4/6 inhibitor were enrolled to ELAINE-1.² Study participants were randomly assigned to receive oral lasofoxifene at a daily dose of 5 mg (n = 52) or intramuscular fulvestrant at 500 mg on days 1, 15, and 29 and every 4 weeks thereafter (n = 51). Treatment continued until progressive disease, intolerable toxicity, death, or study withdrawal.

The primary end point of the trial is progression-free survival (PFS) and key secondary end points that comprise clinical benefit rate (CBR), objective response rate (ORR), and overall survival, as well as safety and tolerability.

For the primary end point, a log-rank test stratifying on visceral metastasis status (yes vs no) and Y537S mutational status (yes vs no) was utilized for primary comparison. Moreover, a 2-sided P value of < .05 was noted to provide a power of 0.90 to detect a HR of 0.5.

At baseline, the mean patient age was 60.8 years (range, 33-84) and most patients were White and had visceral disease. Data from the 2022 ESMO Congress indicated that the median PFS with lasofoxifene was 6.04 months (95% CI, 2.82-8.04) vs 4.04 months (95% CI, 2.93-6.04) with fulvestrant (HR, 0.699; 95% CI, 0.445-1.125; P = .138). Although a numerical improvement was observed with lasofoxifene, the difference was not determined to be statistically significant. The 6-month PFS rates in the investigative and control arms were 53.4% and 37.9%, respectively; the 12-month rates were 30.7% and 14.1%, respectively.

Moreover, lasofoxifene elicited an ORR of 13.2% vs 2.9% with fulvestrant (P = .12). The CBR (≥ 24 weeks) reported in the investigative arm was 36.5% vs 21.6% in the control arm (P = .12).

Regarding safety, most toxicities were noted to be grade 1 or 2 in severity. The most common treatment-emergent adverse effects (AEs) reported in the lasofoxifene and fulvestrant arms, respectively, included nausea (27.5% vs 18.8%), fatigue (23.5% vs 37.5%), arthralgia (21.6% vs 22.9%), hot flush (21.6% vs 10.4%), constipation (15.7% vs 12.5%), dizziness (15.7% vs 4.2%), hypertension (15.7% vs 14.6%), and cough (15.7% vs 10.4%).

Of the 103 patients enrolled to the exploratory analysis, 75% of those who received lasofoxifene and 65% of those who received fulvestrant completed the VAS/VuAS at baseline.¹ Moreover, 23% and 30% of patients, respectively, were noted to have 1 or more moderate or severe symptoms. Among those who completed the assessments at baseline, the median age was 61.5 years. The assessment scales examined dryness, soreness, irritation, and pain.

“Sermonix is pleased with the results of this study, which when combined with the primary ELAINE 1 findings as well as lasofoxifene’s well-researched history of improving vulvovaginal atrophy in postmenopausal women, demonstrate its potential as a novel therapy that clearly fills an unmet medical need,” David Portman, MD, founder and chief executive officer of Sermonix, added in the press release. “We look forward to further investigating lasofoxifene’s efficacy, as a treatment for metastatic breast cancer with fewer negative [AEs] that greatly impact patients’ quality of life.”

References

1. Sermonix’s lasofoxifene improves vaginal/vulvar symptoms relative to fulvestrant in ELAINE 1 study of postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer and an ESR1 mutation. News release. Sermonix Pharmaceuticals, Inc. March 6, 2023. Accessed March 6, 2023. https://finance.yahoo.com/news/sermonix-lasofoxifene-improves-vaginal-vulvar-140000771.html
2. Goetz MP, Plourde P, Stover DG, et al. LBA20 Open-label, randomized study of lasofoxifene (LAS) vs fulvestrant (Fulv) for women with locally advanced/metastatic ER+/HER2- breast cancer (mBC), an estrogen receptor 1 (ESR1) mutation, and disease progression on aromatase (AI) and cyclin-dependent kinase 4/6 (CDK4/6i) inhibitors. Ann Oncol. 2022;33(suppl 7):S1387-S1388. doi:10.1016/j.annonc.2022.08.015