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

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5257-x) contains supplementary material, which is available to authorized users.