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

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 

SUBMITTER: Dromain C 

PROVIDER: S-EPMC6332566 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature