Moffitt Cancer Center, Tampa, Florida, USA
Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA.
Oncologist. 2019 Nov;24(11):1446-1452. doi: 10.1634/theoncologist.2018-0921. Epub 2019 Jun 12.
When carcinoid syndrome (CS) diarrhea (CSD) is inadequately controlled with long-acting somatostatin analogs (SSAs), clinical practice guidelines recommend addition of the tryptophan hydroxylase inhibitor telotristat ethyl (TE). In a 12-week multinational, randomized controlled trial, TE added to SSA reduced peripheral serotonin and the frequency of CSD. We evaluated real-world effectiveness of TE using patient-reported data from a nurse support program over 3 months.
This study used a deidentified data set of patients initiating TE who opted into a nurse support program between March and November 2017 and reported CS symptom burden at baseline and at least one follow-up time point at months 1, 2, and 3. Patients reported demographic and medical history information as well as frequency of bowel movements (BMs) and flushing episodes, severity of nausea, urgency and abdominal pain (0 "no/not at all" to 100 "worst imaginable/very urgent"), and stool form (1 "very hard" to 10 "watery"). Mean changes from baseline in CS symptom burden were reported using paired-sample tests and Wilcoxon signed-rank tests.
Most patients initiating TE enrolled in the nurse program (791/898, 88%), of whom 369 (47%) were included in the analysis. Patients treated with TE reported significant reductions in CSD and other CS symptoms (all < .001). At least half of patients treated with TE experienced ≥30% improvement from baseline in BM frequency and an average reduction of at least two BMs per day within 3 months.
Patients taking SSA therapy showed substantial burden of disease before initiating TE and significant improvements with the addition of TE treatment in this real-world effectiveness study.
Patients with carcinoid syndrome diarrhea uncontrolled by high doses of long-acting somatostatin analogs may be candidates for additional therapy with the tryptophan hydroxylase inhibitor telotristat ethyl. Understanding the real-world prevalence of uncontrolled symptoms and the effectiveness of telotristat ethyl in clinical practice may further support clinical and policy decisions for these patients. This study investigated self-reported carcinoid syndrome symptom burden and improvements among patients initiating telotristat ethyl and participating in a voluntary nurse support program. Disease burden and off-label somatostatin analog treatment before initiating telotristat ethyl were high, and symptoms improved markedly over 1, 2, and 3 months of treatment.
当肠促胰酶肽瘤综合征（CS）腹泻（CSD）不能通过长效生长抑素类似物（SSA）充分控制时，临床实践指南建议加用色氨酸羟化酶抑制剂托特罗司他乙酯（TE）。在一项为期 12 周的多中心、随机对照试验中，TE 加用 SSA 可降低外周血清素和 CSD 的频率。我们使用护士支持计划中患者报告的数据，在 3 个月内评估 TE 的真实世界疗效。
本研究使用了从 2017 年 3 月至 11 月期间选择加入护士支持计划的开始使用 TE 的患者的匿名数据集，并且在基线以及 1、2 和 3 个月时报告 CS 症状负担的至少一个随访时间点。患者报告了人口统计学和病史信息，以及排便次数（BMs）和潮红发作的频率、恶心严重程度、急迫感和腹痛（0“无/完全没有”到 100“最严重/非常急迫”），以及粪便形状（1“非常硬”到 10“水样”）。使用配对样本 t 检验和 Wilcoxon 符号秩检验报告 CS 症状负担从基线的平均变化。
大多数开始使用 TE 的患者（898 例中的 791 例，88%）加入了护士计划，其中 369 例（47%）被纳入分析。接受 TE 治疗的患者报告 CSD 和其他 CS 症状显著减轻（所有 P <.001）。至少一半接受 TE 治疗的患者在 3 个月内经历了至少 30%的 BM 频率改善，并且每天平均减少至少两次 BMs。
在开始使用 TE 之前，接受 SSA 治疗的患者患有明显的疾病负担，并且在这项真实世界疗效研究中添加 TE 治疗后有显著改善。
不能通过长效生长抑素类似物控制的肠促胰酶肽瘤腹泻患者可能是色氨酸羟化酶抑制剂托特罗司他乙酯的附加治疗候选者。了解未控制症状的真实世界发生率以及托特罗司他乙酯在临床实践中的有效性可能会进一步支持这些患者的临床和政策决策。本研究调查了开始接受托特罗司他乙酯治疗并参加自愿护士支持计划的患者的自我报告的肠促胰酶肽瘤综合征症状负担和改善情况。在开始使用托特罗司他乙酯之前，疾病负担和未经批准的生长抑素类似物治疗较高，并且在 1、2 和 3 个月的治疗中症状明显改善。
