Efficacy and Safety Study in Pancreatic or Midgut Neuroendocrine Tumours Having Progressed Radiologically While Previously Treated With Lanreotide Autogel® 120 mg

Median Progression Free Survival (PFS)

Time frame · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

PFS was defined as the time from first injection of lanreotide Autogel® 120 mg every 14 days to progression or death. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured by independent central review using the same imaging technique (computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\]) for each subject throughout the study. The median PFS time was estimated using the Kaplan Meier method for each cohort.

Median Time to Progression

Time frame · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

Time to Progression was defined as time from first injection of lanreotide Autogel® 120 mg every 14 days to progression. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured by independent central review using the same imaging technique (CT scan or MRI) for each subject throughout the study. Median time to progression was estimated using the Kaplan Meier method for each cohort.

Percentage of Subjects Alive and Progression Free

Time frame · Weeks 12, 24, 36, 48, 60 (for both cohorts) and Weeks 72, 84 and 96 (for midgut NET cohort)

The percentage of subjects alive and progression-free was assessed throughout the study up to Week 60 for the panNET cohort and Week 96 for the midgut cohort. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks measured by independent central review using the same imaging technique (CT scan or MRI) for each subject throughout the study. The percentage of subjects alive and progression free was estimated using the Kaplan Meier method for each cohort.

Overall Survival

Time frame · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

Overall survival was defined as the time in months from the first injection of lanreotide Autogel® 120 mg every 14 days to death due to any cause. Median overall survival was estimated using the Kaplan Meier method for each cohort.

Objective Response Rate (ORR)

Time frame · Weeks 12, 24, 36, 48, 60 (for both cohorts) and Weeks 72, 84, and 96 (for midgut cohort)

The ORR was defined as the percentage of subjects who achieve either complete response (CR) or partial response (PR) according to RECIST v1.0 criteria. ORR was evaluated every 12 weeks and results are presented for each cohort.

Disease Control Rate (DCR)

Time frame · Weeks 24 and 48

The DCR was defined as the percentage of subjects who achieved CR plus PR plus Stable Disease (SD), evaluated according to RECIST v1.0 criteria. The DCR at Weeks 24 and 48 is presented for each cohort.

Best Overall Response Rate

Time frame · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

Best overall response was defined as the best response recorded from the initiation of treatment until disease progression, according to RECIST v1.0 evaluation. The percentage of subjects in each response category and those who were non-evaluable (i.e. with no tumour assessment after the start of study treatment) throughout the study are presented for each cohort.

Median Duration of Stable Disease

Time frame · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

Median duration of SD was the time from first injection of lanreotide Autogel® 120 mg every 14 days until the first occurrence of PD by central assessment. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured using the same imaging technique (CT scan or MRI) for each subject throughout the study. Median duration of stable disease was estimated using the Kaplan Meier method for each cohort.

Factors Associated With PFS

Time frame · Screening/Baseline (Day 1)

A univariate cox proportional hazards model was used to assess whether the following factors were associated with PFS: * Hepatic tumour load: \>25% versus reference ≤25% * Tumour Grade: Grade 2 versus reference Grade 1, * Previous surgery of the primary tumour: No versus reference Yes, * Proliferation index Ki67: ≥10% versus reference \<10% * Duration of treatment with lanreotide Autogel® 120 mg every 28 days by category: ≥median value versus reference \<median value, * Age by category: ≥65 years versus reference \<65 years, * Time from diagnosis to study entry by category: ≥3 years versus reference \<3 years, * Time interval between the two CT scans (pre-screening/screening): ≥12 months versus reference \<12 months and * Symptoms (diarrhoea or flushing at baseline): No versus reference Yes. Each factor was assessed for its importance in the Cox model for PFS in a univariate fashion.

Mean Change From Baseline in Number of Stools and Flushing Episodes

Time frame · Baseline (Day 1), Weeks 8,12, 48 and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET cohort)

Symptom control was measured by the total number of stools (diarrhoea) and flushing episodes during the 7 days prior to the visit, reported orally by the subject to the investigator. The mean change from baseline in number of stools and flushing episodes reported at each visit is presented for each cohort.

Mean Change From Baseline in QoL Measured Using EORTC, QLQ-C30 v3.0 (Global Health Status Sub-score)

Time frame · Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort)

Subjects were instructed to complete the 30 questions in the EORTC-QLQ-C30 v3.0 questionnaire at baseline and every 12 weeks throughout the study. The global health status sub-score was assessed using the last 2 questions which represented subject's assessment of overall health \& QoL. Each question was coded on a 7-point scale (1=very poor to 7=excellent). The sub-score was transformed to range from 0-100, with a high score for global health status representing a high QoL. The mean change from baseline in the transformed global health status are presented for the end of study/early withdrawal visit, with a positive change indicating an improvement in QoL.