罗曼娜 3 期：一种增食欲素受体激动剂治疗晚期非小细胞肺癌（NSCLC）伴恶液质患者的 3 期安全性扩展研究。
ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia.
机构信息
ImPACCT - Improving Palliative Aged and Chronic Care through Clinical Research and Translation, Faculty of Health, University of Technology Sydney, Sydney, Australia.
Department of Medicine, Massachusetts General Hospital Cancer Center, Boston.
出版信息
Ann Oncol. 2017 Aug 1;28(8):1949-1956. doi: 10.1093/annonc/mdx192.
BACKGROUND
Cancer anorexia-cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities.
PATIENTS AND METHODS
ROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia. Patients with preserved Eastern Cooperative Oncology Group ≤2 after completing 12 weeks (w) on the ROMANA 1 or ROMANA 2 trials (0-12 weeks) could enroll in ROMANA 3 and continue to receive anamorelin 100 mg or placebo once daily for an additional 12w (12-24 weeks). The primary endpoint of ROMANA 3 was anamorelin safety/tolerability (12-24 weeks). Secondary endpoints included changes in body weight, handgrip strength (HGS), and symptom burden (0-24 weeks).
RESULTS
Of the 703 patients who completed ROMANA 1 and ROMANA 2, 513 patients entered ROMANA 3 (anamorelin, N = 345, mean age 62.0 years; placebo, N = 168; mean age 62.2 years). During ROMANA 3, anamorelin and placebo groups had similar incidences of treatment-emergent adverse events (TEAEs; 52.2% versus 55.7%), grade ≥3 TEAEs (22.4% versus 21.6%), and serious TEAEs (12.8% versus 12.6%). There were 36 (10.5%) and 23 (13.8%) deaths in the anamorelin and placebo groups, respectively; none were drug-related. Improvements in body weight and anorexia-cachexia symptoms observed in the original trials were consistently maintained over 12-24 weeks. Anamorelin, versus placebo, significantly increased body weight from baseline of original trials at all time points (P < 0.0001) and improved anorexia-cachexia symptoms at weeks 3, 6, 9, 12, and 16 (P < 0.05). No significant improvement in HGS was seen in either group.
CONCLUSION
During the 12-24 weeks ROMANA 3 trial, anamorelin continued to be well tolerated. Over the entire 0-24w treatment period, body weight and symptom burden were improved with anamorelin.
CLINICAL TRIAL REGISTRATION NUMBERS
ROMANA 1 (NCT01387269), ROMANA 2 (NCT01387282), and ROMANA 3 (NCT01395914).
背景
癌症恶病质是一种常见于 NSCLC 患者的衰弱状态，其特征是体重减轻、食物摄入减少和生活质量受损。新型选择性 ghrelin 受体激动剂 anamorelin 具有合成代谢和食欲增强作用。
患者和方法
ROMANA 3 是两项 III 期双盲研究的安全性扩展研究，评估了 anamorelin 治疗伴恶病质的晚期 NSCLC 患者的安全性和疗效。在完成 ROMANA 1 或 ROMANA 2 试验（0-12 周）的 12 周后，ECOG 表现状态≤2 的患者可入组 ROMANA 3 并继续接受 anamorelin 100mg 或安慰剂每日一次，持续 12 周（12-24 周）。ROMANA 3 的主要终点是 anamorelin 的安全性/耐受性（12-24 周）。次要终点包括体重、握力（HGS）和症状负担的变化（0-24 周）。
结果
在完成 ROMANA 1 和 ROMANA 2 的 703 例患者中，513 例患者进入 ROMANA 3（anamorelin，N=345，平均年龄 62.0 岁；安慰剂，N=168；平均年龄 62.2 岁）。在 ROMANA 3 期间，anamorelin 和安慰剂组的治疗中出现的不良事件（TEAE；52.2%与 55.7%）、≥3 级 TEAEs（22.4%与 21.6%）和严重 TEAEs（12.8%与 12.6%）发生率相似。anamorelin 组和安慰剂组分别有 36 例（10.5%）和 23 例（13.8%）死亡，均与药物无关。在原始试验中观察到的体重和厌食恶病质症状的改善在 12-24 周内持续保持。与安慰剂相比，anamorelin 在所有时间点（P<0.0001）均从原始试验基线显著增加体重，并在第 3、6、9、12 和 16 周改善厌食恶病质症状（P<0.05）。两组的握力均未见明显改善。
结论
在 12-24 周的 ROMANA 3 试验中，anamorelin 继续具有良好的耐受性。在整个 0-24 周的治疗期间，anamorelin 改善了体重和症状负担。
临床试验注册号
ROMANA 1（NCT01387269）、ROMANA 2（NCT01387282）和 ROMANA 3（NCT01395914）。
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