Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
Texas Oncology Charles A. Sammons Cancer Center at Baylor, Dallas, Texas, USA.
Clin Pharmacol Ther. 2017 Apr;101(4):462-468. doi: 10.1002/cpt.559. Epub 2016 Dec 29.
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 (C ) was available for 182 patients and 294 patients, respectively. Concomitant everolimus administration increased octreotide C 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 C 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 C . Co-administration of everolimus plus octreotide LAR increased octreotide C , which did not impact efficacy.
在 RADIANT-2 试验中，依维莫司联合奥曲肽长效重复制剂（LAR）治疗使晚期功能性神经内分泌肿瘤患者的无进展生存期（PFS）得到了具有临床意义的 5.1 个月的改善。在这项研究中，我们描述了依维莫司联合给药对奥曲肽 LAR 药代动力学的影响及其与疗效和安全性的关系。至少有 182 名患者和 294 名患者分别具有可评估的依维莫司血药浓度和奥曲肽最低血浆浓度（C ）。依维莫司联合给药使奥曲肽 C 增加，依维莫司/安慰剂的几何平均比（GMR）为 1.47（90%置信区间[CI]：1.32-1.64）。无论奥曲肽的暴露量如何，当依维莫司 C 增加两倍时，进展风险始终降低（风险比[HR]：0.74；95%CI：0.46-1.18；HR：0.54；95%CI：0.32-0.92；奥曲肽 6ng/ml 和 4ng/ml 时）。肺部或代谢事件的风险与依维莫司 C 的增加有关。依维莫司联合奥曲肽 LAR 增加了奥曲肽 C ，但对疗效没有影响。
