INTRODUCTION This study evaluated noninferiority of darbepoetin alfa versus placebo for overall survival (OS) and progression-free survival (PFS) in anemic patients with non-small cell lung cancer (NSCLC) treated to a 12.0-g/dL hemoglobin (Hb) ceiling. METHODS Adults with stage IV NSCLC expected to receive ≥2 cycles of myelosuppressive chemotherapy and Hb≤11.0 g/dL were randomized 2:1 to blinded 500 μg darbepoetin alfa or placebo Q3W. The primary endpoint was OS; a stratified Cox proportional hazards model was used to evaluate noninferiority (upper confidence limit for hazard ratio [HR] ˂1.15). Secondary endpoints were PFS and incidence of transfusions or Hb≤8.0 g/dL from week 5 to end of the efficacy treatment period (EOETP). RESULTS The primary analysis set included 2516 patients: 1680 randomized to darbepoetin alfa; 836 to placebo. The study was stopped early per independent Data Monitoring Committee recommendation after the primary endpoint was met with no new safety concerns. Darbepoetin alfa was noninferior to placebo for OS (stratified HR=0.92; 95%CI, 0.83‒1.01) and PFS (stratified HR=0.95; 95%CI, 0.87‒1.04). Darbepoetin alfa was superior to placebo for transfusion or Hb ≤8.0 g/dL from week 5 to EOETP (stratified OR=0.70; 95%CI, 0.57‒0.86; P<.001). Objective tumor response was similar between the arms (darbepoetin alfa, 36.4%; placebo, 32.6%). Incidence of serious adverse events (AEs) was 31.1% in both arms. No unexpected AEs were observed. CONCLUSIONS Darbepoetin alfa dosed to a 12.0-g/dL Hb ceiling was noninferior to placebo for OS and PFS and significantly reduced odds of transfusion or Hb≤8.0 g/dL in anemic patients with NSCLC receiving myelosuppressive chemotherapy.

中文翻译：

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Darbepoetin alfa 对晚期非小细胞肺癌患者化疗所致贫血的长期安全性和有效性的随机、双盲、安慰剂对照、III 期非劣效性研究

引言 本研究评估了在接受 12.0 g/dL 血红蛋白 (Hb) 上限治疗的贫血非小细胞肺癌 (NSCLC) 患者的总生存期 (OS) 和无进展生存期 (PFS) 方面，darbepoetin alfa 与安慰剂的非劣效性. 方法 预计将接受≥2 个周期的骨髓抑制化疗且 Hb≤11.0 g/dL 的 IV 期 NSCLC 成人以 2:1 的比例随机分配至不知情的 500 μg darbepoetin alfa 或安慰剂 Q3W。主要终点是 OS；分层 Cox 比例风险模型用于评估非劣效性（风险比 [HR] ˂ 1.15 的置信上限）。次要终点是 PFS 和输血发生率或 Hb≤8.0 g/dL 从第 5 周到疗效治疗期结束 (EOETP)。结果 主要分析组包括 2516 名患者：1680 名随机分配至 darbepoetin alfa；836 到安慰剂。在满足主要终点且没有新的安全问题后，根据独立数据监测委员会的建议，该研究提前停止。Darbepoetin alfa 在 OS（分层 HR=0.92；95%CI，0.83-1.01）和 PFS（分层 HR=0.95；95%CI，0.87-1.04）方面不劣于安慰剂。从第 5 周到 EOETP，Darbepoetin alfa 在输血或 Hb ≤8.0 g/dL 方面优于安慰剂（分层 OR=0.70；95%CI，0.57-0.86；P<.001）。两组之间的客观肿瘤反应相似（darbepoetin alfa，36.4%；安慰剂，32.6%）。两组的严重不良事件 (AE) 发生率为 31.1%。没有观察到意外的AE。结论：Darbepoetin alfa 剂量达到 12.0-g/dL Hb 上限在 OS 和 PFS 方面不劣于安慰剂，并且显着降低了输血或 Hb≤8 的几率。