Study in Post-menopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer

A Phase IIIb, Multi-center, Open-label Study of RAD001 in Combination With EXemestane in Post-menopausal Women With EStrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Locally Advanced or Metastatic Breast Cancer

This international, multi-center, open-label, single-arm study evaluated the safety and tolerability profile of everolimus in post-menopausal women with HR positive, HER2 negative locally advanced or metastatic breast cancer after documented recurrence or progression following a non-steroidal aromatase inhibitors (NSAI) therapy in Novartis Oncology emergent growth market (EGM) countries.Data was presented by Asian countries vs Non-Asian countries to confirm no difference in safety and efficacy. Summary statistics were presented.

Inclusion Criteria:

• Postmenopausal women with metastatic, recurrent or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.

• Histological or cytological confirmation of hormone-receptor positive (HR+) breast cancer.

• Disease refractory to non-steroidal aromatase inhibitors, defined as:

• Recurrence while on, or within 12 months (365 days) of completion of adjuvant therapy with letrozole or anastrozole, or

• Progression while on, or within one month (30 days) of completion of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer (ABC).

• Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment.

• Patients must have had:

• At least one lesion that could have been accurately measured in at least one dimension

  • 20 mm with conventional imaging techniques or ≥ 10 mm with spiral CT or MRI, or

• Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above.

• Adequate bone marrow, coagulation, liver and renal function.

• ECOG performance status ≤ 2.

Exclusion Criteria:

• Patients overexpressing HER2 by local laboratory testing (IHC 3+ staining or in situ hybridization positive). Patients with IHC 2+ must have a negative in situ hybridization test.
• Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
• Patients with more than one prior chemotherapy line for ABC. A chemotherapy line is an anticancer regimen(s) that contained at least 1 cytotoxic chemotherapy agent, given for a minimum of 21 days.
• Previous treatment with mTOR inhibitors.
• Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
• Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline was not required.
• Patient who were being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A
• History of brain or other CNS metastases, including leptomeningeal metastasis.