Anamorelin Efficacy in Non–Small-Cell Lung Cancer Patients With Cachexia: Insights From ROMANA 1 and ROMANA 2

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2025-02-24 DOI:10.1002/jcsm.13732

Barry J. A. Laird, Richard Skipworth, Philip D. Bonomi, Marie Fallon, Stein Kaasa, Ruben Giorgino, Donald C. McMillan, David C. Currow

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Abstract

Background

Cancer cachexia presents a significant challenge, but the ghrelin agonist anamorelin shows promise as a potential treatment. This study examined whether the baseline systemic inflammatory response (SIR) (measured by the modified Glasgow Prognostic Score [mGPS]), low BMI or greater weight loss, was associated with a differential treatment effect of anamorelin in people with cachexia and non–small-cell lung cancer (NSCLC).

Methods

ROMANA 1 and ROMANA 2 were double-blind, placebo-controlled, randomised Phase 3 trials that enrolled people with inoperable stage III/IV NSCLC with cachexia (≥ 5% weight loss within 6 months or body mass index [BMI] < 20 kg/m²). Patients were randomised 2:1 to anamorelin 100 mg once daily or placebo, for 12 weeks. This is a post hoc analysis of efficacy endpoints (body weight and body composition: lean body mass [LBM] and fat mass [FM]), stratified by baseline mGPS, BMI and weight loss and measured in the modified intent-to-treat pooled population.

Results

Seven hundred ninety-five patients had available data. Anamorelin improved body weight (p < 0.001) and body composition parameters (LBM and FM, p < 0.01) in all mGPS groups. In patients with mGPS = 2, anamorelin increased weight > 5% and improved hand grip strength (HGS) and the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Subscale (FAACT A/CS). In patients with BMI < 20 kg/m² at baseline or weight loss ≥ 10% in the prior 6 months, anamorelin led to significant increases in body weight from baseline (p < 0.001) versus placebo. Patients with weight loss ≥ 10% in the prior 6 months showed the highest improvements in LBM (p < 0.001). Patients with BMI < 20 kg/m² at baseline showed the highest improvements in FM (p < 0.001).

Conclusion

Anamorelin improved body composition parameters in all patients, as well as physical function and symptom burden, particularly in patients with systemic inflammation, BMI < 20 kg/m² and weight loss ≥ 10%. These results highlight that the anabolic mechanisms of anamorelin are more effective in high-risk groups.

Trial Registration

NCT identifiers: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.

Abstract Image

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Anamorelin在非小细胞肺癌恶病质患者中的疗效：来自ROMANA 1和ROMANA 2的见解

癌症恶病质提出了重大的挑战，但胃促生长素激动剂anamorelin显示了作为一种潜在治疗的希望。本研究考察了基线全身性炎症反应（SIR）（通过改进的格拉斯哥预后评分[mGPS]测量）、低BMI或更大的体重减轻是否与阿纳莫瑞林对恶病质和非小细胞肺癌（NSCLC）患者的差异治疗效果有关。方法ROMANA 1和ROMANA 2是双盲、安慰剂对照、随机的3期试验，纳入无法手术的III/IV期非小细胞肺癌伴病毒质患者（6个月内体重减轻≥5%或体重指数[BMI] 20 kg/m2）。患者按2:1随机分配至阿纳莫瑞林100mg每日一次或安慰剂组，持续12周。这是一项疗效终点（体重和身体组成：瘦体重[LBM]和脂肪质量[FM]）的事后分析，通过基线mGPS、BMI和体重减轻进行分层，并在修改后的意向治疗合并人群中进行测量。结果795例患者有资料。Anamorelin改善了所有mGPS组的体重（p < 0.001）和体成分参数（LBM和FM， p < 0.01）。在mGPS = 2的患者中，anamorelin使体重增加5%，并改善了手握力（HGS）和厌食/恶病质治疗功能评估量表（FAACT A/CS）。在基线时BMI为20 kg/m2或前6个月体重减轻≥10%的患者中，与安慰剂相比，阿纳莫瑞林导致体重较基线显著增加（p < 0.001）。前6个月体重减轻≥10%的患者LBM的改善最大（p < 0.001）。基线时BMI为20 kg/m2的患者FM改善程度最高（p < 0.001）。结论阿纳莫瑞林改善了所有患者的身体组成参数，改善了身体功能和症状负担，特别是对全身性炎症、BMI≤20 kg/m2、体重减轻≥10%的患者。这些结果表明，阿纳莫瑞林的合成代谢机制在高危人群中更为有效。试验注册NCT标识符：ROMANA 1: NCT01387269；罗马2:nct01387282。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.