Background
CLARINET: phase 3, randomized, double-blind, placebo-controlled trial in 204 patients with locally advanced or metastatic, nonfunctioning, well or moderately differentiated (grade 1-2), somatostatin-receptor-positive enteropancreatic neuroendocrine tumors of varied origin (pancreas, midgut, hindgut, unknown), randomized 1:1.
Interventions and follow up
Arm A: Lanreotide depot 120 mg deep SC every 28 days
Arm B: Placebo
Primary endpoint: Progression-free survival (PFS)
mFollow up: NR
Arm B: Placebo
Primary endpoint: Progression-free survival (PFS)
mFollow up: NR
Results
Median PFS: not reached vs 18.0mo (Arm A vs B); HR 0.47, 95% CI 0.30-0.73; P<.001
24-month PFS: 65.1% vs 33.0% (Arm A vs B)
24-month PFS: 65.1% vs 33.0% (Arm A vs B)
Adverse events
Overall: Drug-related adverse events 50% vs 28% (Arm A vs B); drug-related serious events 7 vs 1
GI/hepatobiliary: Diarrhea 26% vs 9%; cholelithiasis 10 patients vs 3 patients (Arm A vs B)
GI/hepatobiliary: Diarrhea 26% vs 9%; cholelithiasis 10 patients vs 3 patients (Arm A vs B)
Conclusions
In advanced nonfunctioning enteropancreatic neuroendocrine tumors, lanreotide significantly prolonged progression-free survival versus placebo.
Key Limitations
Largely low-grade, low-tumor-burden, nonfunctioning population; OS not reached and underpowered; benefit in higher-grade or rapidly progressing disease less defined.
Clinical Context
CLARINET led to FDA and EMA approval of lanreotide for unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic NETs (2014). ASCO/ESMO endorse somatostatin analogs as first-line antiproliferative therapy in advanced SSTR-positive NETs.
References
Caplin ME et al, NEJM, 2014, PMID: 25014687
Rinke A et al, JCO, 2009 (PROMID), PMID: 19704057
Rinke A et al, JCO, 2009 (PROMID), PMID: 19704057