Lanreotide versus placebo for tumour reduction in patients with a 68 Ga-DOTATATE PET-positive, clinically non-functioning pituitary macroadenoma (GALANT study): a randomised, multicentre, phase 3 trial with blinded outcome assessment

Background No established medical treatment options currently exist for patients with non-functioning pituitary macroadenoma (NFPMA). Somatostatin analogues may prevent tumour growth, but randomised controlled trials are lacking. In vivo somatostatin receptor assessment with 68 Ga-DOTATATE PET could help in selecting patients for treatment. We aimed to determine the effect of the somatostatin analogue lanreotide on tumour size in patients with a 68 Ga-DOTATATE PET -positive NFPMA. Methods The GALANT study was an investigator -initiated, multicentre, randomised, double-blind, placebo -controlled, parallel -group, phase 3 trial with recruitment at three academic hospitals in the Netherlands. Adult patients with a suprasellar extending NFPMA, either surgery -na & iuml;ve or postoperative remnant >= 10 mm, were eligible for inclusion. Important exclusion criteria were previous sellar radiotherapy and use of dopamine receptor agonists. Somatostatin receptor expression in the NFPMA was determined through 68 Ga-DOTATATE PET/CT, co -registered with MRI. A prede fi ned sample of 44 patients with PET -positive NFPMA were randomly assigned (1:1) to lanreotide acetate 120 mg or placebo, both administered as deep subcutaneous injections every 28 days for 72 weeks. Primary outcome was the change in cranio-caudal tumour diameter measured on pituitary MRI from baseline to end -oftreatment in the intention -to -treat population. Participants, investigators and outcome assessors were masked to treatment allocation. The trial is registered with the Netherlands Trial Registry, NL5136, and EudraCT, 2015-001234-22. Findings Between Nov 3, 2015, and Dec 10, 2019, 49 patients were included in the study. Forty-four patients with a 68 Ga-DOTATATE PET -positive NFPMA were randomly assigned to lanreotide (22 [50 degrees r6]) or placebo (22 [50 degrees r6]). Study treatment was completed in 13 (59%) lanreotide and 19 (86%) placebo participants. The mean (SD) change from baseline in cranio-caudal tumour diameter after treatment was +1 . 2 (2 . 5) mm with lanreotide and +1 . 3 (1 . 5) mm with placebo; adjusted mean difference versus placebo - 0 . 1 mm (95% CI - 1 . 3 to 1 . 2, p = 0 . 93). Adverse events occurred in 22 (100%, 147 events) lanreotide and 21 (95%, 94 events) placebo participants. Gastrointestinal complaints were most common, reported by 18 (82%) lanreotide and 8 (36%) placebo participants. There were no treatment -related serious adverse events. Interpretation Compared with placebo, lanreotide treatment did not reduce tumour size or growth in patients with 68 Ga-DOTATATE PET -positive NFPMA. Funding Ipsen Farmaceutica BV. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).