Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

Phase II Open Label Study of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic, Estrogen Receptor Positive Breast Cancer, After Failure of Tamoxifen and/or Anastrozole and/or Letrozole and/or Fulvestrant and/or Exemestane

This was a multi-center, Israeli phase II open label study evaluating treatment with RAD001 (10 mg daily) combined with letrozole (2.5 mg daily) in postmenopausal women after recurrence or progression on Tamoxifen, Anastrozole or Examestane.

There were no treatments specifically approved after recurrence or progression on AIs. Available options, based on common clinical practice and several treatment guidelines (e.g. NCCN treatment guidelines 2008), included fulvestrant.

Combining RAD001 with letrazole was a rational approach to the treatment of advanced Brest Cancer, offering the potential for inhibition of tumor cell growth\ proliferation and anti angiogenesis while at the same time potentially preventing the development of letrazole resistance.

Screening Period:

Postmenopausal women with estrogen receptor positive, locally advanced or metastatic breast cancer whose disease was refractory to hormonal therapy and had a documented recurrence or progression on last therapy for their breast cancer with either tamoxifen, anastrozole, letrozole, fulvestrant or exemestan were screened for eligibility within 28 days prior to treatment Day 1.

Treatment Period:

Patients started receiving everolimus (10 mg daily oral dose) combined with letrozole (2.5 mg daily oral dose) tablets from treatment Day 1. Study treatment continued until disease progression, intolerable toxicity or consent withdrawal. Dose adjustment (reduction, interruption or possible dose re-escalation to starting dose) could be done based on the safety findings. Tumor assessments were performed every 12 weeks until disease progression. In order to confirm response at least four weeks after first observation, additional scans to determine a complete response (CR) or partial response (PR) or stable disease (SD) were performed. Patients were followed for safety until 28 days after study treatment discontinuation.

Post Treatment Follow up for Survival:

Patients were followed for survival every 3 months for up to 3 years. Survival information could be obtained via phone and information was documented in the source documents.

Inclusion Criteria:

• Postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer after documented recurrence or progression on Tamoxifen, Anastrozole or Examestane.

  • Refractory disease to hormonal therapy is defined as:

    1. Recurrence while on, or within 12 month of end of, adjuvant treatment with Tamoxifen , Anastrozole, or Exemestane.
    2. Recurrence while on, or within 24 month of end of, adjuvant treatment with Letrozole.
    3. Progression while on Tamoxifen, Anastrozole or Exemestane treatment for locally advanced or metastatic breast cancer.

Exclusion Criteria:

• Prior use of chemotherapy and letrozole for Advanced Breast Cancer and mTOR inhibitors as the last anticancer treatment prior to study entry.
• Patients must have radiological evidence of recurrence or progression on last therapy prior to study entry.