Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study

Abstract

In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n=101) or placebo (n=103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n=41; placebo, n=47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs.

The LARO-MEN1 study: a longitudinal clinical experience with octreotide Long-Acting Release in patients with Multiple Endocrine Neoplasia type 1 Syndrome

“…They were subsequently maintained under the same treatment and observed up to 72 months afterwards by means of biochemical and instrumental assessment. The outcomes of this study are in agreement with the results of several large clinical trials, which have shown the efficacy of somatostatin analogues in the treatment of sporadic and advanced NETs (33)(34)(35)(36) and reinforce data of the retrospective study by Ramundo et al on a larger group of patients with early MEN1-related NETs (20 subjects) treated with octreotide LAR 30 mg administered i.m. every 28 days as first-line therapy for a mean follow-up period of about 40 months (38).…”

“…The mechanisms of these effects are not completely understood, but recent evidences indicate that they rely, at least in part, on the inhibition of proliferative signaling pathways, activation of apoptosis, and modulation of angiogenesis (16,41,42). Data from international clinical trials have demonstrated the efficacy of octreotide LAR in controlling symptoms related to hormonal hypersecretion by functioning NETs and carcinoid syndrome, but also to control and slow down tumor growth even in functioning tumors in progression (PROMID and CLARINET studies) (33)(34)(35)(36), with an extension of progression-free survival, while preclinical and clinical studies provide conflicting results on their antitumor effect in asymptomatic lesions dis-…”

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

“…Lanreotide was active irrespective of Ki-67, tumor burden and primary site. The open-label extension study of the CLARINET study confirmed the antiproliferative activity in progressive disease patients on placebo who crossed over to openlabel lanreotide (Caplin et al 2016). Most patients had stable disease before therapy in the CLARINET study, whereas the disease status was unknown in the PROMID study.…”

99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors

“…According to Clarinet study (Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors), usage of long-acting SSA was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 < 10%) [33,34]. This positive antineoplastic result was not seen in our very small group of patients with MTC and NEC (n = 7) that received "cold" SSA.…”