Evaluation of the Effects of Pasireotide LAR Administration on Lymphocele Prevention after Axillary Node Dissection for Breast Cancer: Results of a Randomized Non-Comparative Phase 2 Study

Objective
The aim of this study was to assess the efficacy (response rate centered on 80%) of a somatostatin analog with high affinity for 4 somatostatin receptors in reducing the postoperative incidence of symptomatic lymphocele formation following total mastectomy with axillary lymph node dissection.
Setting
This prospective, double-blind, randomised, placebo-controlled, phase 2 trial was conducted in two secondary care centres.
Participants
All female patients for whom mastectomy and axillary lymph node dissection were indicated were eligible for the study, including patients who had received neo-adjuvant chemotherapy. Main exclusion criteria were related to diabetes, cardiac insufficiency, disorder of cardiac conduction or hepatic failure.
Interventions
Patients were randomised to receive one injection of either prolonged-release pasireotide 60 mg or placebo (physiological serum), which were administered intramuscularly 7 to 10 days before the scheduled surgery. The study was conducted in a double-blind manner.
Primary and Secondary Outcome Measures
The primary outcome measure was the percentage of patients who did not develop post-operative axillary symptomatic lymphoceles during the 2 postoperative months. Secondary endpoints were the total quantity of lymph drained, duration and daily volume of drainage and aspirated volumes of lymph.
Results
Ninety-one patients were randomised. Ninety patients were evaluable: 42 patients received pasireotide, and 48 patients received placebo. The mean estimated response rate were 62.4% (95% Credibility Interval [CrI]: 48.6%-75.3%) in the treatment group and 50.2% (95% CrI: 37.6%-62.8%) in the placebo group. Overall safety was comparable across groups, and one serious adverse event occurred. In the treatment group, one patient with known insulin-depe*ndent diabetes required hospitalization for hyperglycaemia.
Conclusions
With this phase 2 preliminary study, even if our results indicate a trend towards a reduction in symptomatic lymphocele, pre-operative injection of pasireotide failed to achieve a response rate centered on 80%. Pharmacokinetics analysis suggests that effect of pasireotide could be optimised.
Trial Registration
ClinicalTrials.gov NCT01356862

研究目的
本研究旨在评估对4种生长抑素受体具有高亲和力的生长抑素类似物（somatostatin analog），在伴腋窝淋巴结清扫的全乳房切除术后，降低症状性淋巴囊肿形成术后发生率的疗效（预设响应率目标为80%）。
研究场所
本项前瞻性、双盲（double-blind）、随机（randomised）、安慰剂对照（placebo-controlled）II期临床试验（phase 2 trial）于两家二级医疗中心开展。
研究对象
所有符合乳房切除术联合腋窝淋巴结清扫指征的女性患者均符合本研究入组标准，包括曾接受新辅助化疗的患者。主要排除标准涉及糖尿病、心功能不全、心脏传导异常或肝衰竭。
干预措施
患者被随机分配接受单次注射缓释帕瑞肽（pasireotide）60mg或安慰剂（生理血清），于计划手术前7至10天肌内注射给药。本研究采用双盲设计。
主要与次要结局指标
主要结局指标为术后2个月内未发生术后腋窝症状性淋巴囊肿的患者占比。次要终点包括淋巴引流量总量、引流时长、每日引流量及抽吸淋巴液量。
研究结果
共纳入91例随机分组患者，其中90例可进行疗效评估：42例接受帕瑞肽治疗，48例接受安慰剂治疗。治疗组的平均估算响应率为62.4%（95%可信区间[Credibility Interval, CrI]：48.6%~75.3%），安慰剂组为50.2%（95% CrI：37.6%~62.8%）。两组总体安全性相当，仅发生1例严重不良事件：治疗组中1例已知为胰岛素依赖型糖尿病的患者因高血糖需住院治疗。
研究结论
本项II期初步研究结果显示，尽管观察到症状性淋巴囊肿发生率降低的趋势，但术前注射帕瑞肽并未达到预设的响应率目标80%。药代动力学分析提示，帕瑞肽的治疗效果可进一步优化。
试验注册
ClinicalTrials.gov NCT01356862