A Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in Advance Breast Cancer.

The reference therapy (control arm) used in the course of this trial was the combination arm
of everolimus plus exemestane. The investigational therapies in the context of this study
were everolimus monotherapy and capecitabine monotherapy. All treatments were taken orally
until disease progression, intolerable toxicity or withdrawal of patient's informed consent.
Patients were randomly assigned with equal allocation to one of the treatment arms:

1. Exemestane (25mg daily) in combination with everolimus (10mg daily)

2. Everolimus (10mg daily)

3. Capecitabine (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest
period in 3-weeks cycles.

Treatment assignment was stratified by the presence of visceral disease (yes vs. no).
Visceral refered to lung, liver, heart, ovary, spleen, kidney, adrenal gland, malignant
pleural or pericardial effusion or malignant ascites.

Key Inclusion Criteria:

-Women with locally advanced, recurrent, or metastatic breast cancer along with
confirmation of estrogen-receptor positive (ER+). Measurable disease defined as at least
one lesion ≥ 10 mm by CT or MRI that can be accurately measured in at least one dimension
(CT scan slice thickness ≤ 5 mm) OR • Bone lesions: lytic or mixed (lytic + blastic) in the
absence of measurable disease as defined above

Key Exclusion Criteria:

-Patients who received more than one chemotherapy line. Patients with only non-measurable
lesions other than lytic or mixed (lytic and blastic) bone metastasis.Previous treatment
with exemestane, mTOR inhibitors, PI3K inhibitors or AKT inhibitors