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

Dromain C, Pavel ME, Ruszniewski P, Langley A, Massien C, Baudin E, Caplin ME (2019)


Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 19

Article Number: 66

Journal Issue: 1

DOI: 10.1186/s12885-018-5257-x

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 (TGR 0 ); 12-24 weeks before randomization versus baseline; each treatment visit versus baseline (TGR Tx-0 ); between consecutive treatment visits (TGR Tx-Tx ). To assess TGR as a measure of prognosis, PFS was compared for TGR 0 subgroups stratified by optimum TGR 0 cut-off; a multivariate analysis was conducted to identify prognostic factors for PFS. Results: TGR 0 revealed tumors growing during pre-treatment (median [interquartile range] TGR 0 : 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 TGR 0-12 of - 2.9 [- 5.1, - 0.8], p = 0.008), a difference that was maintained at most subsequent visits. TGR 0 > 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, TGR 0 , 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.

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How to cite

APA:

Dromain, C., Pavel, M.E., Ruszniewski, P., Langley, A., Massien, C., Baudin, E., & Caplin, M.E. (2019). Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors. BMC Cancer, 19(1). https://dx.doi.org/10.1186/s12885-018-5257-x

MLA:

Dromain, Clarisse, et al. "Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors." BMC Cancer 19.1 (2019).

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