The purpose of this Phase III study was to confirm the value of adding everolimus to weekly paclitaxel and trastuzumab as treatment of HER2-overexpressing metastatic breast cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
719
Everolimus was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).
Everolimus placebo was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).
Trastuzumab, 2 mg/kg weekly was used intravenously.
Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - Full Population
PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first. This was assessed in the full patient population.
Time frame: date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months
Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - (Hormone Receptor (HR)-Negative Population
PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first. This was assessed in the HR-negative patient population.
Time frame: date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months
Overall Survival (OS) - Full Population
OS is defined as the time from date of randomization to the date of death due to any cause. For patients with documented progression, survival follow up was performed either by telephone or clinic visit at least every 3 months. Additional survival updates were requested prior to interim or final analysis or prior to providing data to the health authorities. This was assessed in the full patient population.
Time frame: up to about 76 months
Overall Survival (OS) - HR-negative Population
OS is defined as the time from date of randomization to the date of death due to any cause. For patients with documented progression, survival follow up was performed either by telephone or clinic visit at least every 3 months. Additional survival updates were requested prior to interim or final analysis or prior to providing data to the health authorities. This was assessed in the HR-negative patient population.
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Paclitaxel, 80 mg/m2 weekly was used intravenously.
University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.
Mobile, Alabama, United States
Ironwood Cancer and Research Centers
Chandler, Arizona, United States
Highlands Oncology Group
Fayetteville, Arkansas, United States
Comprehensive Blood and Cancer Center Dept. of CBCC (2)
Bakersfield, California, United States
St. Jude Heritage Medical Group Virginia Crosson Cancer Center
Fullerton, California, United States
University of California at Los Angeles Dept. of UCLA
Los Angeles, California, United States
Ventura County Hematology and Oncology
Oxnard, California, United States
Cancer Care Associates Medical Group Dept. of CCA
Redondo Beach, California, United States
Santa Barbara Hematolgy Oncology Medical Group Dept.ofSantaBarbaraHem/Onc
Santa Barbara, California, United States
Central Coast Medical Oncology Corporation Onc Dept
Santa Maria, California, United States
...and 130 more locations
Time frame: up to about 76 months
Overall Response Rate (ORR) - Full Population
ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST. This was assessed in the full patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.
Time frame: up to about 23 months
Overall Response Rate (ORR) - HR-negative Population
ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST. This was assessed in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.
Time frame: up to about 23 months
Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - Full Population
CBR is defined as the percentage of participants whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST. This was assessed in the full patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.
Time frame: up to about 23 months
Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - HR-negative Population
CBR is defined as the percentage of participants whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST. This was assessed in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.
Time frame: up to about 23 months
Time to Overall Response Based on Investigator - Full Population
Time to overall response defined as the time between date of randomization until first documented response Complete reseponse (CR) or partial response (PR) ), according to RECIST. This was assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.
Time frame: up to about 23 months
Time to Overall Response Based on Investigator - HR-negative Population
Time to overall response defined as the time between date of randomization until first documented response Complete reseponse (CR) or partial response (PR) ), according to RECIST. This was assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.
Time frame: up to about 23 months
Overall Response (OR) - Full Population
OR applies only to patients whose best OR was CR or PR. Start date = date of first documented response (CR or PR) and end date = date of documented response (CR or PR) and end date = date of event defined as the first documented progression or death due to underlying cause. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.
Time frame: up to about 23 months
Overall Response (OR) - HR-negative Population
OR applies only to patients whose best OR was CR or PR. Start date = date of first documented response (CR or PR) and end date = date of documented response (CR or PR) and end date = date of event defined as the first documented progression or death due to underlying cause. This was assessed in the HR-negative patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.
Time frame: up to about 23 months
Everolimus Blood Level Concentrations at Steady States for Everolimus
Blood levels at steady states for everolimus 10 mg/day and 5 mg/day. Only valid samples are included. Some patients had dose reduction to 5 mg daily dose therefore the everolimus blood concentration for them have been summarized separately. Cycle = 28 days
Time frame: predose, 2 hours post-dose at Cycle 2/Day 1, Cycle 2/Day 15, Cycle 2/ Day 22
Paclitaxel Plasma Concentrations
Blood levels at steady states for everolimus/placebo
Time frame: Cycle 2/Day 15 (Pre-infusion and end of infusion)
Trastuzumab Serum Concentrations
Blood levels at steady states for everolimus/placebo
Time frame: Cycle 4/Day 1 (Pre-infusion and end of infusion)
Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - Full Population
Time to definitive deterioration of the ECOG PS by one category of the score from baseline will be performed. Baseline is the last available assessment on or before randomization date. A deterioration is considered definitive if no improvements in the ECOG PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed.
Time frame: up to about 56 months
Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - HR-negative Population
Time to definitive deterioration of the ECOG PS by one category of the score from baseline will be performed. Baseline is the last available assessment on or before randomization date. A deterioration is considered definitive if no improvements in the ECOG PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed.
Time frame: up to about 56 months