- Women (18 years of age) with metastatic breast cancer not amenable to curative
treatment by surgery or radiotherapy.
- Documentation of histological or cytological confirmation of estrogen receptor
positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
- Documentation of menopausal status: postmenopausal subjects are eligible
pre-menopausal subjects with ovarian radiation or concomitant treatment with an LH-RF
agonist/antagonist must have a plasma/serum estradiol assay of <20 pg/mL at screening
within 7 days prior to randomization. Negative pregnancy test is also required at
screening. Agreement to use adequate method of contraception as recommended by their
- Subjects with bone dominant disease with at least 2 skeletal metastases identified at
baseline by bone scintigraphy and confirmed by computed tomography (CT)/magnetic
resonance imaging (MRI).
- Subjects must have received at least one line of hormonal therapy in the metastatic
- Subjects who are eligible as per the Investigator's assessment and according to the
local label for treatment with exemestane and everolimus as a second line or greater
of hormone therapy in a metastatic setting.
- Subjects must have experienced recurrent/progressive disease following treatment with
a non-steroidal aromatase inhibitor (letrozole or anastrozole) in an adjuvant or
- Subjects must have experienced no more than two skeletal-related events (SREs) prior
to study entry defined as: external beam radiotherapy (EBRT) for bone pain,
pathological bone fracture (excluding major trauma), spinal cord compression and/or
orthopedic surgical procedure. Subjects with no prior SREs are not permitted.
- Subjects must be on therapy with bisphosphonates or denosumab for at least 1 month
before start of study treatment.
- Asymptomatic or mildly symptomatic breast cancer.
- Adequate hematological, liver and kidney function
- Subjects with any of the following cancers:
- Inflammatory breast cancer
- Bilateral breast cancer or a history of 2 distinct breast cancers.
- Patients with immediately life-threatening visceral disease for whom chemotherapy is
preferred treatment option
- Subjects who have either received chemotherapy for metastatic disease or are
considered by the treating investigator to be appropriate candidates for chemotherapy
as current treatment for metastatic breast cancer are excluded. Chemotherapy
administered for adjuvant/neo adjuvant disease is acceptable provided it was
administered at least 1 year prior to study entry.
- Subjects who received prior treatment or are already receiving everolimus treatment
prior to study entry are not eligible
- Subjects with known or history of brain metastases or leptomeningeal disease:
subjects with neurological symptoms must undergo a contrast CT scan or MRI of the
brain within 28 days prior to randomization to exclude active brain metastasis.
Imaging of the central nervous system (CNS) is otherwise not required.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female
Time to opiate use for cancer pain
Time to pain progression
Time to cytotoxic chemotherapy
Radiological progression-free survival (rPFS)
Frequency of abnormalities in laboratory examinations
Frequency of abnormalities in Adverse Events
Frequency of abnormalities in new primary malignancies