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Clin Pharmacol Ther. 2017 Apr;101(4):462-468. doi: 10.1002/cpt.559. Epub 2016 Dec 29.

Effect of everolimus on the pharmacokinetics of octreotide long-acting repeatable in patients with advanced neuroendocrine tumors: An analysis of the randomized phase III RADIANT-2 trial.

Author information

1
Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
2
Texas Oncology Charles A. Sammons Cancer Center at Baylor, Dallas, Texas, USA.
3
Novartis Pharmaceuticals Corporation, Basel, Switzerland.
4
Novartis Pharmaceuticals Corporation, Florham Park, New Jersey, USA.
5
University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Abstract

In the RADIANT-2 trial, addition of everolimus to octreotide long-acting repeatable (LAR) exhibited a clinically meaningful 5.1-month improvement in progression-free survival (PFS) in patients with advanced functional neuroendocrine tumors. In this study, we characterized the effects of everolimus co-administration on octreotide LAR pharmacokinetics and its relationship with efficacy and safety. At least one evaluable blood everolimus and plasma octreotide predose minimum concentration (Cmin ) was available for 182 patients and 294 patients, respectively. Concomitant everolimus administration increased octreotide Cmin with a geometric mean ratio (everolimus/placebo) of 1.47 (90% confidence interval [CI] = 1.32-1.64). Risk for progression was consistently reduced when everolimus Cmin was increased twofold, regardless of octreotide exposure (hazard ratio [HR] = 0.74; 95% CI = 0.46-1.18; HR = 0.54; 95% CI = 0.32-0.92 for 6 ng/mL and 4 ng/mL octreotide, respectively). Risk for pulmonary or metabolic events was associated with increased everolimus Cmin . Co-administration of everolimus plus octreotide LAR increased octreotide Cmin , which did not impact efficacy.

PMID:
28032910
DOI:
10.1002/cpt.559
[Indexed for MEDLINE]

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