Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET

Progression-free Survival (PFS) Per Local Radiological Review

Time frame · Once 80 PFS events had occurred aproximately after 24 months

PFS per RECIST 1.0. (Response Evaluation Criteria in Solid Tumors). PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.

Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR

Time frame · Once 80 PFS events had occurred

Consisted of monitoring and recording the rate, type, severity, and causal relationship of adverse events (AEs) and serious AEs (SAEs) to treatment. The safety analysis was based mainly on the frequency of AEs or SAEs and on the number of laboratory values that fell outside of pre-determined range.

Objective Response Rate (ORR) as Per Radiology Review

Time frame · Once 80 PFS events had occurred

Objective response was determined by the local radiologist according to the RECIST Version 1.0. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). This is also referred to as Overall response rate. CR: Disappearance of all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameter of all target lesions recorded at or after baseline.

Duration of Response (DoR)

Time frame · Once 80 PFS events had occurred

80 PFS are expected after approximately 24 months. Kaplan Meier was initially planned to be used to depict duration of response by treatment group and by stratum. Later based on the mode of action of everolimus and pasireotide and based on study experience, only a low number of objective responses per RECIST were expected. Therefore, protocol was amended to only list duration of response, and confirmed responses were flagged in the listing. Hence, statistical analyses were not planned and such data are not available for the following table.

Overall Survival (OS) Using Kaplan Meier Method

Time frame · Once 80 PFS events had occurred

Overall survival was defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival was to be censored at the date of last contact.

PFS and the Predictive Probability of Success in Phase III

Time frame · Once 105 PFS events had occurred occurred

105 PFS events expected after approximately 36 months

Disease Control Rate (DCR) as Per Radiology Review

Time frame · Once 80 PFS events had occurred

Disease control rate is the percentage of patients with a best overall response of CR or PR or stable disease (SD) determined by the local radiologist according to the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) Version 1.0. CR: Disappearance of all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameter of all target lesions recorded at or after baseline. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD). PD: Any progression ≤ 18 weeks after randomization (and not qualifying for CR, PR or stable disease SD.

Summary of Pharmacokinetics (PK) for Everolimus for AUClast

Time frame · Cycle 2 Day 1

Summary of Pharmacokinetics (PK) for Everolimus for CL/F

Time frame · Cycle 2 Day 1

Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin

Time frame · Cycle 2 Day 1

Summary of Pharmacokinetics (PK) for Everolimus for Tmax

Time frame · Cycle 2 Day 1