Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy

Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.

Time frame: from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months)

Population: The full analysis set (FAS) consisted of all patients who received at least one dose of everolimus.

Duration of overall response applies only to patients whose best overall response was complete response (CR) or partial response (PR): * Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. * Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression. Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions

Time frame: from date of first documented confirmed response to time to progression, at least 3 months

Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of everolimus. Only those patients whose best overall response was complete response (CR) or partial response (PR) were included in this analysis.

Duration of overall response applies only to patients whose best overall response was complete response (CR) or partial response (PR): * Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. * Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression. Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions

Time frame: from date of first documented confirmed response to time to progression, at least 3 months

Population: Very low number of patients demonstrated a partial response, the median duration of response as per central review has not been calculated.

The effect of Octreotide Depot on the trough concentrations of everolimus was assessed at Cycle 1 Day 15.

Time frame: Cycle 1 Day 1, Cycle 2 Day 1

Population: Full Analysis Set (FAS) is consisted of all patients who received at least one dose of everolimus. Patients with Octreotide Depot pharmacokinetic samples, with nonzero concentration, at Cycle 1 Day 1 or Cycle 2 Day 1 were included.

For all patients in both strata, a blood sample for everolimus trough level determination will be collected immediately prior to the everolimus administration on Cycle 1 Day 15, Cycle 2 Day 1, and every month thereafter. A treatment cycle was defined as 28 days of consecutive daily treatment with everolimus and treatment continued until tumor progression. It is critical that patients not take their daily everolimus dose before the sample is drawn.

Time frame: Cycle 1 Day 15

Population: Full Analysis Set (FAS) is consisted of all patients who received at least one dose of everolimus. Patients with everolimus pharmacokinteic samples, with nonzero concentration, at Cycle 1 Day 15 were included

Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Time frame: on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month

Population: The safety population consists of all patients who received at least one dose of everolimus and had at least one post-baseline safety assessment.

Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Time frame: on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month

Population: The safety population consists of all patients who received at least one dose of everolimus and had at least one post-baseline safety assessment.

Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.

Time frame: from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months)

Population: Full Analysis Set (FAS) was consisted of all patients who received at least one dose of everolimus.

Overall survival measures the time of survival , with any response or disease progression, until death. The OS is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact. In each treatment stratum, the Kaplan-Meier estimate of the overall survival function was constructed.

Time frame: from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012

Population: The full analysis set consisted of all patients who received at least one dose of everolimus.

Overall survival measures the time of survival , with any response or disease progression, until death. The OS is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact. In each treatment stratum, the Kaplan-Meier estimate of the overall survival function was constructed.

Time frame: from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012

Population: The full analysis set consisted of all patients who received at least one dose of everolimus.

Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The Kaplan-Meier estimate of the PFS survival function was constructed. Median PFS was obtained and displayed along with 95% confidence intervals.

Time frame: from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010

Population: The full analysis set (FAS) consisted of all patients who received at least one dose of everolimus.

Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The Kaplan-Meier estimate of the PFS survival function was constructed. Median PFS was obtained and displayed along with 95% confidence intervals.

Time frame: from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010

Population: The full analysis set (FAS) consisted of all patients who received at least one dose of everolimus.