背景:癌症恶病质的特征是体重减轻(BW)和厌食。Anamorelin(ANAM)是一种选择性ghrelin受体激动剂,具有增强食欲的合成代谢作用。ONO-7643-05试验表明,ANAM增加了日本人群的瘦体重并改善了厌食症。然而,ANAM患者的临床结局尚未报道.
方法:我们调查了无法切除的患者的临床结局,先进,或复发性胃肠道癌(结直肠癌,胃,或胰腺癌),在2017年4月至2022年8月期间接受ANAM治疗。恶病质被定义为存在厌食症,并且在6个月内损失≥5%的BW。为了评估对ANAM的反应,在3周内停用ANAM的患者被排除.对ANAM的反应定义为在每3周评估时维持或增加BW和从基线改善食欲。我们还收集了有关停止ANAM的原因以及临床因素与ANAM反应之间的相关性的数据。对所有接受ANAM的患者进行ANAM的安全性分析。
结果:本研究纳入了74例患者(男性49例,女性25例),年龄中位数为67.1岁(范围,36-83).原发肿瘤为结直肠癌27例(36.5%),胃癌20例(27.0%),胰腺癌27例(36.5%)。东部肿瘤协作组的表现状态为10分之0(13.5%),44人中的1人(59.5%),和≥2/20(27.0%)。既往化疗方案数为0/20(27.0%),1/22(29.7%),32人中≥2人(43.2%)。28例患者在3周内停用ANAM,原因如下:15例患者出现低度(1级或2级)不良事件,在三个肠梗阻,三级疲劳合一,一种进行性疾病,审查了六次的后续行动,三个原因不明。ANAM应答者的比例为63.6%(95%置信区间,47.8-77.6%)。在基线特征中,年龄≥75减弱ANAM反应(p=0.03)。ANAM应答者在化疗时表现出比无应答者更好的疾病控制(75.0%vs.37.5%,p=0.02)。
结论:在临床实践中,ANAM可以改善胃肠道肿瘤恶病质患者的预后。
BACKGROUND: Cancer cachexia is characterized by the loss of body weight (BW) and anorexia. Anamorelin (ANAM) is a selective ghrelin receptor agonist with appetite-enhancing anabolic action. The ONO-7643-05 trial demonstrated that ANAM increased lean body mass and improved anorexia in a Japanese population. However, the clinical outcomes of patients on ANAM have not yet been reported.
METHODS: We investigated the clinical outcomes of patients with unresectable, advanced, or recurrent gastrointestinal cancer (colorectal, gastric, or pancreatic cancer) who were treated with ANAM between April 2017 and August 2022. Cachexia was defined as the presence of anorexia and a loss of ≥ 5% of BW within 6 months. To evaluate the response to ANAM, the patients who had discontinued ANAM within 3 weeks were excluded. Response to ANAM was defined as maintenance of or increase in BW and improved appetite from baseline at every 3-week evaluation. We also collected data on the reasons for the discontinuation of ANAM and the correlation between clinical factors and ANAM response. Safety analysis of ANAM was performed for all patients who received ANAM.
RESULTS: Seventy-four patients were included in this study (49 males and 25 females), with a median age of 67.1 years (range, 36-83). The primary tumors were colorectal cancer in 27 (36.5%), gastric cancer in 20 (27.0%), and pancreatic cancer in 27 (36.5%). The Eastern Cooperative Oncology Group performance status was 0 in 10 (13.5%), 1 in 44 (59.5%), and ≥ 2 in 20 (27.0%). The number of previous chemotherapy regimens was 0 in 20 (27.0%), 1 in 22 (29.7%), and ≥ 2 in 32 (43.2%). ANAM was discontinued within 3 weeks in 28 patients for the following reasons: low-grade (grade 1 or 2) adverse events in 15 patients, ileus in three, grade 3 fatigue in one, progressive disease in one, censored follow-up in six, and unknown reasons in three. The proportion of ANAM responders was 63.6% (95% confidence interval, 47.8-77.6%). Among baseline characteristics, age ≥ 75 attenuated the ANAM response (p = 0.03). ANAM responders showed better disease control with chemotherapy than non-responders (75.0% vs. 37.5%, p = 0.02).
CONCLUSIONS: ANAM may improve the outcomes of patients with gastrointestinal cancer cachexia in clinical practice.