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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Neuroendocrine Tumor | Research article

Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors

Authors: Clarisse Dromain, Marianne E. Pavel, Philippe Ruszniewski, Alison Langley, Christine Massien, Eric Baudin, Martyn E. Caplin, on behalf of the CLARINET Study Group

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Lanreotide depot/autogel antitumor activity in intestinal/pancreatic neuroendocrine tumors (NETs) was demonstrated in the phase-3 CLARINET study (NCT00353496), based on significantly prolonged progression-free survival (PFS) versus placebo.

Methods

During CLARINET, patients with metastatic intestinal/pancreatic NETs received lanreotide depot/autogel 120 mg or placebo every 4 weeks for 96 weeks. Imaging data (response evaluation criteria in solid tumors [RECIST] v1.0, centrally reviewed) were re-evaluated in this post hoc analysis of tumor growth rate (TGR) in NETs. TGR (%/month) was calculated from two imaging scans during relevant periods: pre-treatment (TGR0); 12–24 weeks before randomization versus baseline; each treatment visit versus baseline (TGRTx-0); between consecutive treatment visits (TGRTx-Tx). To assess TGR as a measure of prognosis, PFS was compared for TGR0 subgroups stratified by optimum TGR0 cut-off; a multivariate analysis was conducted to identify prognostic factors for PFS.

Results

TGR0 revealed tumors growing during pre-treatment (median [interquartile range] TGR0: lanreotide 2.1%/month [0.2; 6.1]; placebo 2.7%/month [0.15; 6.8]), contrary to RECIST status. TGR was significantly reduced by 12 weeks with lanreotide versus placebo (difference in least-square mean TGR0–12 of − 2.9 [− 5.1, − 0.8], p = 0.008), a difference that was maintained at most subsequent visits. TGR0 > 4%/month had greater risk of progression/death than ≤4%/month (hazard ratio 4.1; [95% CI 2.5–6.5]; p < 0.001); multivariate analysis revealed lanreotide treatment, progression at baseline, TGR0, hepatic tumor load, and primary tumor type were independently associated with PFS.

Conclusions

TGR provides valuable information on tumor activity and prognosis in patients with metastatic intestinal/pancreatic NETs, and identifies early lanreotide depot/autogel antitumor activity.

Trial registration

Retrospective registration, 18 July 2006; EudraCT: 2005–004904-35; ClinicalTrials.gov: NCT00353496.
Appendix
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Metadata
Title
Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors
Authors
Clarisse Dromain
Marianne E. Pavel
Philippe Ruszniewski
Alison Langley
Christine Massien
Eric Baudin
Martyn E. Caplin
on behalf of the CLARINET Study Group
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5257-x

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