Characteristics of the included trials
| Author, year | Study design | Inclusion criteria | Participant count | Intervention given | Previous treatment | Primary endpoints |
|---|---|---|---|---|---|---|
| Bidard et al. [16], 2022 | Randomized, open-label, phase III trial (NCT03778931) | - Postmenopausal women or men- Age: 18 years or older- Histologically or cytologically proven ER+/HER2– breast adenocarcinoma- Either locoregionally recurrent or metastatic disease | 477; elacestrant (n = 239), SOC (n = 238) | Elacestrant dosing:- 400 mg orally once daily- Reductions to 300 mg or 200 mg daily permitted for toxicityStandard of care (SOC) treatment:- Per investigator’s choice (fulvestrant, anastrozole, letrozole, or exemestane monotherapy)- Dosed according to the labeling | - CDK4/6 inhibitors (progression on previous treatment was required) in combination with fulvestrant or an AI- One chemotherapy regimen in the advanced/metastatic setting was permitted | - PFS in all patients, assessed by BICR using standard RECIST v1.1 criteria—PFS in patients with detectable ESR1 mutation, assessed by BICR using standard RECIST v1.1 criteria |
| Bardia et al. [17], 2021 | Multicenter, open-label, four-part, dose-escalation study (NCT02338349) | - Postmenopausal women, age ≥ 18 years- ER+ (≥ 1% staining by immunohistochemistry)- HER2− locally advanced, inoperable, and/or metastatic breast adenocarcinoma- ECOG performance status 0–1 | 50 | The RP2D was 400 mg of elacestrant once daily | Part A–C:- Required ≤ 2 prior lines of chemotherapy for advanced/metastatic breast cancer- Required ≥ 6 months of prior ET (no limit) in any settingPart D:- Required ≤ 1 prior line of chemotherapy for advanced/metastatic breast cancer- Required ≥ 2 prior lines of ET for advanced/metastatic breast cancer (single agent/in combination)- Required one prior line of treatment with fulvestrant with documented progression and prior CDK4/6i | Frequency of DLTs during the first 28 days of treatment |
| Jager et al. [18], 2020 | Phase 1b, open-label, non-randomized (NCT02650817) | - Postmenopausal women, prior bilateral ovariectomy- Histologically proven ER+ (defined as ≥ 1% staining by immunohistochemistry), HER2− ABC (either inoperable primary breast cancer or mBC)- ECOG performance status: 0–2 | 16 | - Initially enrolled and treated with 400 mg elacestrant capsule once daily (QD)- Second cohort of 8 patients enrolled and treated with 200 mg elacestrant capsule QD for 14 days to assess target engagement of a lower dose-After 14 days, the dose was escalated to 400 mg QD | - 6 or more months of 1–3 lines of systemic endocrine treatment for mBC- Prior CDK4/6 inhibitor therapy were allowed | Percentage difference in FES uptake in tumor lesions (up to a maximum of 20 lesions) after 14 days of treatment with elacestrant compared to baseline |
AI: aromatase inhibitor; BICR: blinded independent central review; DLTs: dose-limiting toxicities; ER+: estrogen receptor-positive; FES: fluoroestradiol; PFS: progression-free survival; RP2D: recommended phase 2 dose; HER2–: HER2-negative
