Endocrine Abstracts (2019) 68 OC1 | DOI: 10.1530/endoabs.68.OC1

Longitudinal biomarker changes during treatment of functional midgut neuroendocrine tumours with lanreotide autogel: CALM-NET study results

Tahir Shah1, Martyn Caplin2, Mohid S Khan3, Aude Houchard4, Kate Higgs5 & Tim Meyer6


1Queen Elizabeth Hospital Birmingham, Birmingham, UK; 2Royal Free Hospital, London, UK; 3University Hospital of Wales, Cardiff, UK; 4Ipsen Pharma, Boulogne-Billancourt, France; 5Ipsen Ltd, Slough, UK; 6University College Longon, London, UK


Background: CALM-NET (EudraCT 2013-002194-22; NCT02075606), a prospective, exploratory study, evaluated enumeration of pre-treatment circulating tumour cells as a predictor of symptomatic response to lanreotide autogel (LAN) in patients with functional midgut neuroendocrine tumours (NETs). Here, we describe the effect of LAN on biomarkers.

Methods: Patients, ≥18 years, with functional, well- or moderately-differentiated midgut NETs were treated with LAN 120 mg every 28 days for up to 52 weeks. Urinary and plasma 5-hydroxyindoleacetic acid (5HIAA), chromogranin A (CgA) and neurokinin A (NKA) were measured; correlations between plasma and urinary 5HIAA (baseline; Weeks 4, 16, 24; end-of-study [EOS]) were assessed. Correlations between plasma 5HIAA/CgA, plasma 5HIAA/NKA and changes in biomarkers according to symptomatic response to LAN (≥50% reduction in diarrhoea/flushing episodes, or decrease in flushing severity [mild, moderate, severe] by ≥1 level) were assessed (post-hoc analyses).

Results: Fifty patients enrolled; 40 (80%) completed. All biomarkers decreased during LAN treatment (Table 1). There was a strong correlation between plasma and urinary 5HIAA (Spearman correlation coefficients ≥0.87 [P<0.001] at all timepoints). Correlation coefficients were ≥0.68 for plasma 5HIAA/CgA and ≥0.57 for plasma 5HIAA/NKA (P<0.0001 at all timepoints). Median (95% CI) reduction in plasma 5HIAA between baseline and EOS/early withdrawal was greater in LAN symptomatic responders (−91.5 [−159.0, −16.0] ng/ml, n=34) than non-responders (−9.0 [−267.0, 79.0] ng/ml, n=5), though small sample sizes preclude statistical conclusions.

Table 1
Median (95% CI) biomarker level
BaselineChange from baseline to Week 4Change from baseline to EOS/early withdrawal
Urinary 5HIAA (μmol/day)121.7 (92.5, 196.9) [n=42]−26.4 (−64.3, −9.9) [n=38]−41.4 (−87.1, −15.5) [n=33]
Plasma 5HIAA (ng/ml)425.0 (256.0, 507.0) [n=47]−109.5 (−172.0, −54.0) [n=46]−83.0 (−159.0, −38.0) [n=41]
CgA (×ULN)3.9 (3.1, 5.5) [n=48]−1.7 (−2.3, −1.0) [n=46]−1.0 (−1.7, −0.2) [n=40]
Neurokinin A (pg/ml)31.0 (23.0, 42.0) [n=47]−5.0 (−10.0, −2.0) [n=44]−7.0 (−14.0, −3.0) [n=39]
Ipsen-funded study.

Conclusions: All biomarker levels decreased during LAN treatment in patients with functional midgut NETs. The study provides preliminary evidence supporting plasma 5HIAA as a biomarker for assessing response to LAN, avoiding the need for 24-h urinary 5HIAA testing, which can be cumbersome and unreliable.

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