TPS 43 ADELA: A Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial of Elacestrant + Everolimus vs Elacestrant + Placebo in ER+/HER2– Advanced Breast Cancer Patients With ESR1-Mutated Tumors Progressing on Endocrine Therapy

Publication
Article
Miami Breast Cancer Conference® Abstracts Supplement42nd Annual Miami Breast Cancer Conference® - Abstracts
Volume 39
Issue 4
Pages: 24-25

TPS 43 ADELA: A Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial of Elacestrant + Everolimus vs Elacestrant + Placebo in ER+/HER2– Advanced Breast Cancer Patients With ESR1-Mutated Tumors Progressing on Endocrine Therapy

TPS 43 ADELA: A Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial of Elacestrant + Everolimus vs Elacestrant + Placebo in ER+/HER2– Advanced Breast Cancer Patients With ESR1-Mutated Tumors Progressing on Endocrine Therapy

Background

ET plus CDK4/6 inhibitor (CDK4/6i) is the standard of care (SOC) in first-line estrogen receptor–positive/HER2-negative (ER+/HER2–) advanced breast cancer; however, tumors eventually develop resistance. Constitutive activation in PI3K/AKT/mTOR pathway can contribute to endocrine resistance in breast cancer. The ESR1 mutation is a common type of acquired resistance that emerges in 40% to 50% of patients in the metastatic setting after prolonged aromatase inhibitor exposure. There is an unmet need for novel therapeutic approaches to overcome resistance mechanisms and improve outcomes in patients with ER+/HER2– advanced breast cancer with ESR1-mutated tumors progressing after ET plus CDK4/6i. Elacestrant is a next-generation oral SERD that binds to ER-alpha, inducing its degradation. In the phase 3 EMERALD study (NCT03778931), elacestrant improved progression-free survival (PFS) vs SOC ET in patients with ESR1-mutated tumors (HR, 0.55; 95% CI, 0.39-0.77; P = .0005). Differences were notable among patients who received prior ET plus CDK4/6i 12 months or more; median PFS with elacestrant was 8.6 months vs 1.9 months with SOC ET (HR, 0.41; 95% CI, 0.26-0.63). Crosstalk between ER and PI3K/AKT/mTOR pathways provides a rationale for evaluating elacestrantwith everolimus (an mTORC1 inhibitor). The phase 3 ADELA study (NCT06382948) compares elacestrant plus everolimus vs. elacestrant plus placebo in patients with ER+/HER2– advanced breast cancer with ESR1-mutated tumors progressing on ET plus CDK4/6i.

Materials and Methods

ADELA is an international, multicenter, double-blind, placebo-controlled phase 3 trial. Eligible patients are adults (>18 years) with ER+/HER2– advanced breast cancer with ESR1-mutated tumors, previously treated with 1 to 2 lines of ET for advanced breast cancer, and evidence of disease progression on prior ET plus CDK4/6i for advanced after 6 months or more. Patients receiving CDK4/6i-based adjuvant therapy are eligible (disease progression must be confirmed after 12 months or more of treatment but less than 12 months following CDK4/6i completion). Other criteria include adequate organ function and ECOG performance status of 0 to 1. Exclusion criteria include prior chemotherapy for advanced breast cancer and active uncontrolled/symptomatic brain metastasis. Patients will be randomized 1:1 to 28-day cycles of elacestrant at 345 mg plus everolimus at 7.5 mg by mouth or elacestrant at 345 mg plus placebo by mouth until disease progression or unacceptable toxicity, based on dose determined in phase 1/2 ELEVATE trial (NCT05563220). Patients will receive dexamethasone mouthwash during the first 8 weeks. Stratification factors are the presence of visceral metastases (yes vs no) and duration of prior CDK4/6i (≥12 months vs <12 months). The primary objective will evaluate BIRC-based PFS.Secondary end points included investigator-assessed PFS, overall survival, overall response rate, clinical benefit rate, duration of response, time to response, the best percentage change in tumor burden, safety, and health-related quality of life.

Status

Planned enrollment is 240 patients; recruitment is ongoing.

Articles in this issue

10 AI as a Bridge: Can ChatGPT Help Patients Understand Their Breast Radiology Reports?
10 AI as a Bridge: Can ChatGPT Help Patients Understand Their Breast Radiology Reports?
12 Gut Microbiome Composition and Pathological Complete Response After Chemotherapy in Breast Cancer: Insights From a Pilot Study
12 Gut Microbiome Composition and Pathological Complete Response After Chemotherapy in Breast Cancer: Insights From a Pilot Study
13 Preliminary Analysis of Change During Treatment of Financial Toxicity and Quality of Life in Breast Cancer Patients
13 Preliminary Analysis of Change During Treatment of Financial Toxicity and Quality of Life in Breast Cancer Patients
15 Utilizing Circulating Tumor Cells to Guide HER2-Directed Therapy in IHC/FISH-Negative HER2+ Metastatic Breast Cancer
15 Utilizing Circulating Tumor Cells to Guide HER2-Directed Therapy in IHC/FISH-Negative HER2+ Metastatic Breast Cancer
16 A Miami Hospital’s Infrastructure to Help Decrease Late-Stage Breast Cancer Diagnosis and Improve Health Equity
16 A Miami Hospital’s Infrastructure to Help Decrease Late-Stage Breast Cancer Diagnosis and Improve Health Equity
17 Salmonella and the Breast: A Literature Review of Salmonella-Induced Breast Abscesses
17 Salmonella and the Breast: A Literature Review of Salmonella-Induced Breast Abscesses
18 Tolerability of First-Line Treatment With Ribociclib for Metastatic Breast Cancer Using 2 Large US Data Sources
18 Tolerability of First-Line Treatment With Ribociclib for Metastatic Breast Cancer Using 2 Large US Data Sources
20 Impact of Ribociclib Dose Reduction on Efficacy in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast
20 Impact of Ribociclib Dose Reduction on Efficacy in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast
21 Distant Disease-Free Survival Across Key Subgroups From the Phase 3 NATALEE Trial of Ribociclib Plus a Nonsteroidal Aromatase Inhibitor in Patients With HR+/HER2− Early Breast Cancer
21 Distant Disease-Free Survival Across Key Subgroups From the Phase 3 NATALEE Trial of Ribociclib Plus a Nonsteroidal Aromatase Inhibitor in Patients With HR+/HER2− Early Breast Cancer
22 Efficacy and Safety of Ribociclib + Nonsteroidal Aromatase Inhibitor in Younger Patients With HR+/HER2− Early Breast Cancer in NATALEE
22 Efficacy and Safety of Ribociclib + Nonsteroidal Aromatase Inhibitor in Younger Patients With HR+/HER2− Early Breast Cancer in NATALEE
23 Clinical Outcomes in Patients With HR+/HER2− Early Breast Cancer By Prior Systemic Treatment: A Subgroup Analysis of the NATALEE Trial
23 Clinical Outcomes in Patients With HR+/HER2− Early Breast Cancer By Prior Systemic Treatment: A Subgroup Analysis of the NATALEE Trial
TPS 24 Phase Ib Dose-Finding Study of [177Lu]Lu-NeoB + Ribociclib + Fulvestrant in Patients With ER+/HER2− Advanced Breast Cancer With GRPR Expression With Early Relapse FromAdjuvant Endocrine Therapy or Progression on ET + CDK4/6i for ABC
TPS 24 Phase Ib Dose-Finding Study of [177Lu]Lu-NeoB + Ribociclib + Fulvestrant in Patients With ER+/HER2− Advanced Breast Cancer With GRPR Expression With Early Relapse FromAdjuvant Endocrine Therapy or Progression on ET + CDK4/6i for ABC
TPS 25 Phase 1/2 Study of the Novel Radioligand Therapy [177Lu]Lu-NeoB Plus Capecitabine in Patients With ER+/HER2− Advanced Breast Cancer (ABC) With GRPR Expression After Progression on Prior Endocrine Therapy Plus a CDK4/6 Inhibitor for ABC
TPS 25 Phase 1/2 Study of the Novel Radioligand Therapy [177Lu]Lu-NeoB Plus Capecitabine in Patients With ER+/HER2− Advanced Breast Cancer (ABC) With GRPR Expression After Progression on Prior Endocrine Therapy Plus a CDK4/6 Inhibitor for ABC
26 Risk of Recurrence in Real-World NATALEE- and monarchE-Eligible Populations of Patients With HR+/HER2− Early Breast Cancer in an Electronic Health Record-Derived Database
26 Risk of Recurrence in Real-World NATALEE- and monarchE-Eligible Populations of Patients With HR+/HER2− Early Breast Cancer in an Electronic Health Record-Derived Database
27 Elacestrant vs Standard of Care in ER+, HER2- Advanced or Metastatic Breast Cancer With ESR1-Mutated Tumors: ESR1 Allelic Frequencies and Clinical Activity From the Phase 3 EMERALD Trial
27 Elacestrant vs Standard of Care in ER+, HER2- Advanced or Metastatic Breast Cancer With ESR1-Mutated Tumors: ESR1 Allelic Frequencies and Clinical Activity From the Phase 3 EMERALD Trial
Recent Videos
Breast oncologist Jade E. Jones, MD, says she tries to send patients with BRCA-mutant HR-positive TNBC to clinical trials that use PARP inhibitors.
Following progression on a CDK4/6 inhibitor, ascertaining the endocrine sensitivity of HR-positive/HER2-negative disease may inform sequential treatment.
T-DXd improved progression-free survival over standard chemotherapy among patients with HR-positive/triple-negative breast cancer in DESTINY-Breast04.
The use of chemotherapy trended towards improved recurrence-free intervals in older patients with high-risk tumors as determined via the MammaPrint assay.
Use of a pharmacist-directed resource appears to improve provider confidence and adverse effect monitoring for patients undergoing infusion therapy.
Reshma L. Mahtani, DO, describes how updates from the DESTINY-Breast09, ASCENT-04, and VERITAC-2 trials may shift practices in the breast cancer field.
Multidisciplinary care can help ensure that treatment planning does not deviate from established guidelines for inflammatory breast cancer management.
Related Content