Effect of lanreotide depot (LAN) on 5-hydroxyindoleacetic acid (5HIAA) and chromogranin A (CgA) in gastroenteropancreatic neuroendocrine (GEP NET) tumors: Correlation with tumor response and progression-free survival (PFS) from the phase III CLARINET study.

Abstract

4095 Background: 5HIAA or CgA are biomarkers in some GEP NETs. We present posthoc analyses using prospectively collected urinary 5HIAA and serum CgA data from CLARINET. Methods: Adults with moderately or well differentiated, nonfunctioning (no symptoms of carcinoid syndrome), locally advanced or metastatic GEP NETs were randomized to LAN 120mg or placebo (PBO) every 4 weeks (wks) for 96 wks. Tumor response evaluated centrally (RECIST 1.0) and PFS were assessed by treatment. Biochemical response was defined as baseline > upper limit of normal (ULN, 41.6µmol/d 5HIAA; 98.1µg/L CgA) and ≥50% decrease from baseline to ≤ULN value on study. CgA analyses excluded gastrinoma patients (pts). Results: 48% (82/171) (45LAN; 37PBO) and 66% (129/195) (65LAN, 64PBO) of pts had > ULN baseline 5HIAA and CgA. In those pts with no radiologic progression, significantly greater reductions in 5HIAA (Table) and CgA were observed in LAN vs PBO pts at all assessments (all P< 0.05). PFS was significantly prolonged in LAN 5HIAA responders vs nonresponders (median not reached vs 22.1 months, P= 0.0076) but was not significantly different in PBO 5HIAA responders vs nonresponders. There were no significant differences in PFS by CgA response (responders vs nonresponders) in either LAN or PBO pts. Conclusions: These data suggest that serotonin is secreted by nonfunctioning tumors, but does not reach the threshold required for clinical carcinoid symptoms. Monitoring 5HIAA and CgA may be useful during LAN treatment of nonfunctional GEP NETs. Clinical trial information: NCT00353496. [Table: see text]