Study Evaluating Abemaciclib + Aromatase Inhibitors in HR+, HER2- Advanced Breast Cancer Patients (HERMIONE-7)

Hormone receptor positive tumors represent the most common form of breast cancer and account for most of the deaths from the disease. Endocrine therapy (ET) represents the main initial therapeutic strategy for these patients and has been associated with significant clinical benefits in the majority of them. Key-Topics for rationale: * Fulvestrant, an Estrogen-Receptor (ER) antagonist with no known agonist effects, suppresses estrogen signaling by binding to and degrading the ER. Fulvestrant was approved as a monthly 250 mg dosing regimen based on TTP data demonstrating non-inferiority versus anastrozole in postmenopausal women whose advanced breast cancer had progressed during prior anti-estrogen therapy. * The international CONFIRM trial compared Fulvestrant 500 mg (High-Dose Fulvestrant HD-FUL: Fulvestrant 500 mg every month with an additional 500 mg loading dose on Day 14 of the first month) with the monthly 250 mg dose and demonstrated that HD-FUL mg was associated with improved progression-free survival (PFS) and overall survival (OS) in postmenopausal women with ER-positive (ER+) advanced breast cancer whose disease had recurred or progressed after prior endocrine therapy. * The FALCON study evaluated the efficacy and safety of HD-FUL in comparison to anastrozole in HR+, HER2- recurrent or metastatic breast cancer (MBC) patients. Median duration of PFS with HD-FUL was 16·6 months (95% CI 13·83-20·99) in the whole population and 22.3 months (95% CI 16·62-32·79) in the non-visceral one. Grade 3 or worse adverse events were reported by 51 (22%) of 228 patients receiving HD-FUL. * Palbociclib, Abemaciclib and Ribociclib + Fulvestrant are superior to Fulvestrant alone in terms of PFS (PALOMA-3: 9.5 vs 4.6 months; MONARCH-2: 16.4 vs 9.3; MONALEESA-3: 20.5 vs 12.8) in patients who have received prior endocrine therapy for advanced disease or have relapsed during or within 1 month from adjuvant therapy. * A descriptive study analyzed European treatment patterns for HR-positive MBC patients in real-world clinical practice in the years 2004 - 2013 showed that Fulvestrant was the initial therapy for advanced disease in 0.8 - 2.6% of the patients. However, the ongoing real-world GIM-13 AMBRA study showed that in Italy this percentage has grown up to 30%. At the moment, no data are available regarding the activity of CDK 4/6 inhibitors in patients treated with HD-FUL as 1st-line therapy, nor are there ongoing trials in this setting. The aim of this study is to describe the activity of Abemaciclib + aromatase inhibitors (AIs - letrozole or anastrozole) in HD-FUL pre-treated MBC patients in terms of Clinical Benefit Rate (CBR). This is a phase II, single-arm, open-label, multicenter study in HR+, HER2- advanced breast cancer patients who have received HD-FUL as first-line endocrine treatment for their metastatic disease. Patients will receive aromatase inhibitors plus Abemaciclib.. Abemaciclib will be administered orally at 150 mg twice daily until evidence of disease recurrence or other discontinuation criteria are met, whichever occurs first, together with AIs, as per specific product instructions. The Simon's optimal two-stage design will be used for the conduction of the trial.