Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with CDK4/6 inhibitors (CDK4/6i) + ET, in order to spare the adverse events related to chemotherapy.
Anyway, the efficacy of endocrine monotherapy in patients progressing on first line therapy is low, because of the occurrence of endocrine resistance mechanisms, like the HR loss and the switch to HR-negative subtype, caused by the selective pressure of first line therapy; furthermore, biomarkers for patient selection are missing.
Recently, the 16a-\[18F\]fluoro-17b-estradiol positron emission tomography (\[18F\]FES-PET) demonstrated a sensitivity and specificity of 86% in estrogen receptor expression prediction; therefore it is a promising tool to select patients progressing on CDK4/6i + ET without HR loss.
Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with target cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) + ET, in order to spare the adverse events related to chemotherapy.
Anyway, the efficacy of endocrine monotherapy in patients progressing on first line therapy is low, because of the occurrence of endocrine resistance mechanisms, like the Hormon Receptor (HR) loss and the switch to HR-negative subtype, caused by the selective pressure of first line therapy; furthermore, biomarkers for patient selection are missing.
Recently, the 16a-\[18F\] fluoro-17b-estradiol positron emission tomography (\[18F\] FES-PET) demonstrated a sensitivity and specificity of 86% in estrogen receptor expression prediction; therefore it is a promising tool to select patients progressing on CDK4/6i + ET without HR loss.
The combination of endocrine agent, namely fulvestrant 250 mg plus anastrozole 1 mg (an aromatase inhibitor), demonstrated to provide an overall survival benefit in patients with Hormon Receptor positive Breast Cancer only in first line setting but not in patients progressing to ET. However, meanwhile, fulvestrant 500 mg was demonstrated to be superior to fulvestrant 250 mg in 2nd line setting, and oral SERDs (e.g. Elacestrant, Camizestrant) were demonstrated to be superior in terms of Progression Free Survival to fulvestrant 500 mg in patients progressing on ET, in the subgroup of patients with estrogen receptor 1 gene (ESR1) mutations.
Hypothesis: there is a strong rationale to assess the safety and the activity of Elacestrant plus exemestane in patients with pre-treated HR+ and Human Epidermal Growth Factor Receptor 2 negative (HER2-) metastatic breast cancer and at least 50% of \[18F\]FES-avid measurable lesions, using \[18F\]FES PET/CT to evaluate the early response to treatment.
Must be at least 18 years old;
Must have a histologically- or cytologically-proven diagnosis of carcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy
Must be appropriate candidates for endocrine therapy (no visceral crisis, highly symptomatic disease or rapidly progressing disease)
Measurable disease
Prior treatment with fulvestrant, elacestrant or investigational SERD or ER antagonist in metastatic or early disease (e.g., D-0502, GDC-0810, GDC-0927, GDC-9545, G1T-48, LSZ102, AZD9496, SAR439859, ZN-c5, H3B-6545, bazedoxifene, lasofoxifene)
Prior treatment with tamoxifen or SERD alone or combined with CDK4/6i in metastatic setting
Any other endocrine therapy < 14 days before first dose of study drug
Any prior treatment after first line with CDK4/6i in metastatic setting
Single group
elacestrant and exemestane
Drugelacestrant 345 mg die and exemestane 25 mg die
6-month Progression Free Survival (PFS) rate per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
Adverse Event (AE) per Common Terminology Criteria for Adverse Events (CTCAE) 5.0
Median Overall Survival (OS)
Overall Response Rate (ORR) per RECIST v1.1
Median QoL (QLQ-C30) change from baseline to week 8 of treatment
Median QoL change from baseline to week 8 of treatment measured by EORTC QLQ-C30 av.4 questionarie
6-months Progression Free Survival (PFS) rate per RECIST 1.1 by ESR1/PIK3CA mutation, ER≥50%/PgR≥50% expression, APOBEC+/HRD+/PAM-50 luminal status
Progression Free Survival (PFS) rate per RECIST v1.1 by genomic and epigenomic alterations at baseline and after 4 weeks of treatment
Click on the lead sponsor to view all of their trials.
