Novel Tumor Growth Rate Analysis in the Randomized CLARINET Study Establishes the Efficacy of Lanreotide Depot/Autogel 120 mg with Prolonged Administration in Indolent Neuroendocrine Tumors

Abstract

Introduction: Tumor quantity while receiving cancer therapy is the sum of simultaneous regression of treatment-sensitive and growth of treatment-resistant fractions at constant rates. Exponential rate constants for tumor regression/decay (d) and growth (g) can be estimated. Previous studies established g as a biomarker for overall survival; g increases after treatment cessation, can estimate doubling times, and can assess treatment effectiveness in small cohorts by benchmarking to large reference data sets. Using this approach, we analyzed data from the clinical trial CLARINET, evaluating lanreotide depot/autogel 120 mg/4 weeks (LAN) for treatment of neuroendocrine tumors (NETs). Methods and Materials: Computed tomography imaging data from 97 LAN- and 101 placebo-treated patients from CLARINET were analyzed to estimate g and d. Results: Data from 92% of LAN- and 94% of placebo-treated patients could be fit to one of the equations to derive g and d (p