Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumours

Median Progression-Free Survival (PFS) Time in Subjects Randomised to Lanreotide in the Double-Blind Phase or Open-Label Treatment Phase, Assessed by Central Review

Time frame · Up to a maximum of 33 months

PFS for subjects randomised in the lanreotide group, assessed by central review using Response Evaluation Criteria In Solid Tumours Version 1.1 (RECIST v1.1) criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during either the double-blind phase, or the open-label treatment phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

Median PFS Time in the Double-Blind Phase, Assessed by Central Review

Time frame · Up to a maximum of 15 months

PFS was assessed by central review using RECIST v1.1 criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during the double-blind phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

Median PFS Time in the Double-Blind Phase, Assessed by Local Review

Time frame · Up to a maximum of 15 months

PFS was assessed by local review using RECIST v1.1 criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during the double-blind phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

Objective Response Rate (ORR) in the Double-Blind Phase

Time frame · Up to a maximum of 15 months

ORR was assessed by central review and local review using RECIST v1.1 criteria every 12 weeks, defined as the percentage of subjects who achieved a best overall response of complete response or partial response in the double-blind phase.

Time to Treatment Failure (TTF) in the Double-Blind Phase

Time frame · Up to a maximum of 15 months

TTF was defined as the time from randomisation to disease progression using RECIST v1.1, death, consent withdrawn, an adverse event, protocol deviations, lost to follow-up, the appearance of carcinoid syndrome or other hormone related syndrome necessitating the initiation of SSAs (rescue octreotide and/or long-acting release SSA), or initiation of anticancer treatment in the double-blind phase. The distribution of TTF times were estimated using the Kaplan-Meier product limit method.

Mean Change From Baseline in the Biomarker Chromogranin A (CgA) in the Double-Blind Phase and Open-Label Treatment Phase

Time frame · Baseline, Weeks 8, 12, 24, and 48, and post-treatment in the double-blind phase (a maximum of 15 months); Baseline, Weeks 12, 24, and 48, and post-treatment in the the open-label treatment phase (a maximum of 33 months)

Blood samples were collected to determine plasma CgA. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide). The x of upper limit of normal (ULN) was calculated as raw value/ULN.

Percentage of Subjects With a Decrease of CgA ≥30% From Baseline at Week 8 in the Double-Blind Phase and Open-Label Treatment Phase

Time frame · Baseline and Week 8 in the double-blind phase; Baseline and Week 8 in the open-label treatment phase

Measured in subjects with an elevated CgA at baseline (≥2 x ULN). Blood samples were collected to determine plasma CgA. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

Mean Changes From Baseline in Quality of Life (QoL), as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Global Health Status/QoL Score

Time frame · Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months)

The EORTC QLQ-C30 (V3.0) consisted of 30 questions. The final 2 questions were related to global health status/QoL, with responses requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The global health status/QoL scale ranges in score from 0 to 100. A high score for the global health status/QoL scale represents a high QoL, thus, an increase in score represents an increase in QoL. 95% Clopper-Pearson confidence intervals were estimated using the exact method for binomial distributions. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

Percentage of Subjects Who Experienced QoL Deterioration

Time frame · Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months)

QoL deterioration was defined by a decrease from baseline in EORTC QLQ-C30 Global Health Status/QoL Score of at least 10 points. The EORTC QLQ-C30 (V3.0) consisted of 30 questions. The final 2 questions were related to global health status/QoL, with responses requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The global health status/QoL scale ranges in score from 0 to 100. A high score for the global health status/QoL scale represents a high QoL, thus, an increase in score represents an increase in QoL. 95% Clopper-Pearson confidence intervals were estimated using the exact method for binomial distributions. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

Mean Changes From Baseline in Urinary 5-hydroxyindoleacetic Acid (5-HIAA) Levels in the Double-Blind Phase and Open-Label Treatment Phase

Time frame · Baseline, Weeks 8, 12, 24, and 48, and post-treatment in the double-blind phase (a maximum of 15 months); Baseline, Weeks 12, 24, and 48, and post-treatment in the the open-label treatment phase (a maximum of 33 months)

Measured in subjects with an elevated 5-HIAA at baseline (≥2 x ULN). The assessment of urinary 5-HIAA required subjects to collect their urine for the 24 hour period prior to the study visit. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide). The x of ULN was calculated as raw value/ULN.