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.

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 <.001 in most data sets). LAN-treated patients demonstrated significantly slower g than placebo recipients (P=.00315), a difference of 389 days in doubling times. No significant difference was observed in d. Over periods of LAN administration up to 700 days, g did not change appreciably. Simulated analysis with g as the endpoint showed a sample size of 48, sufficient to detect a difference in median g with 80% power.

CONCLUSION: Although treatment of NETs with LAN can affect tumor shrinkage, LAN primarily slows tumor growth rather than accelerates tumor regression. Evidence of LAN efficacy across tumors was identified. The growth-retarding effect achieved with LAN was sustained for a prolonged period of time.

IMPLICATIONS FOR PRACTICE: The only curative treatment for NETs is surgical resection; however, due to frequent late diagnosis, this is often impossible. Because of this, treatment of NETs is challenging and often aims to reduce tumor burden and delay progression. A novel method of analysis was used to examine data from the CLARINET trial, confirming LAN is effective at slowing tumor growth and extending progression-free survival (PFS). By providing the expected rate and doubling time of tumor growth early in the course of treatment, this method of analysis has the potential to guide physicians in their management of patients with NETs.