Phase 3
N=724
Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole
Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT00863655 ↗Enrolled (actual)
724
Serious AEs
27.1%
Results posted
Aug 2012
Primary outcome: Primary: Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. — 6.93; 2.83 months — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Everolimus (Drug); Exemestane (Drug); Everolimus Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Dec 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. |
6.93; 2.83 | <0.0001 sig |
| SECONDARY Overall Survival (OS) by Number of Deaths |
267; 143 | — |
| SECONDARY Overall Survival (OS) by Median |
30.98; 26.55 | — |
| SECONDARY Overall Response Rate (ORR) |
9.5; 0.4 | — |
| SECONDARY Clinical Benefit Rate (CBR) |
33.4; 18.0 | — |
| SECONDARY Proportion of Patients With no Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Using Kaplan-Meier |
0.84; 0.87; 0.74; 0.80; 0.64; 0.67 | — |
| SECONDARY Patient-reported Outcomes (PROs): Time to Deterioration of PRO Scores Using Kaplan Meier - EORTC QLQ-C30 |
4.53; 4.40; 4.83; 4.37; 6.93; 6.93 | — |
| SECONDARY Proportion of Patients With Having no Overall Response Based on Investigator Assessment |
0.96; 1.00; 0.93; 1.00; 0.92; 1.00 | — |
| SECONDARY Duration of Response (Among Participants With Best Overall Response of CR or PR) Estimated Per Kaplan-Meier |
8.21; NA | — |
| SECONDARY Everolimus Concentrations at Week 4 |
16.04; 46.50 | — |
| SECONDARY Exemestane Concentrations at Week 4 |
0.63; 0.43; 23.16; 13.30 | — |
| SECONDARY Estradiol Plasma Concentrations |
5.62; 4.09; 3.50; 5.17 | — |
Summary
There are no treatments specifically approved after recurrence or progression on a non steroidal aromatase inhibitors (NSAI). In light of the need for new treatment options for postmenopausal women after failure of prior NSAI therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment with exemestane + everolimus to exemestane + placebo in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAI.
Eligibility Criteria
Inclusion Criteria
- Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
- Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
- Postmenopausal women.
- Disease refractory to non steroidal aromatase inhibitors (NSAI),
- Radiological or clinical evidence of recurrence or progression on or after the last systemic therapy prior to randomization.
- Patients must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease as defined above.
Exclusion Criteria
- HER2-overexpressing patients
- Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.).
- Patients who received more than one chemotherapy line for Advanced Breast Cancer.
- Previous treatment with exemestane or mTOR inhibitors.
- Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
- Radiotherapy within four weeks prior to randomization
- Currently receiving hormone replacement therapy,
Other protocol-defined inclusion/exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT00863655). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.