South Paris University, Institut Gustave Roussy, Villejuif, France.
J Clin Oncol. 2011 Nov 20;29(33):4442-51. doi: 10.1200/JCO.2011.37.2623. Epub 2011 Oct 17.
To evaluate the efficacy and safety of dulanermin combined with paclitaxel and carboplatin (PC) and bevacizumab (PCB) as first-line treatment for advanced or recurrent non-small-cell lung cancer (NSCLC).
Patients with squamous NSCLC and/or CNS metastases received PC every 3 weeks alone (arm 1) or with dulanermin 8 mg/kg for 5 days (arm 2). Patients with nonsquamous NSCLC received PCB alone (arm 3) or with dulanermin 8 mg/kg for 5 days (arm 4) or 20 mg/kg for 2 days (arm 5). The primary end point was the objective response rate (ORR).
Overall, 213 patients were randomly assigned (arm 1, n = 41; arm 2, n = 39; arm 3, n = 42; arm 4, n = 40; arm 5, n = 41). The ORR in arms 1 to 5 was 39% (95% CI, 24% to 56%), 38% (95% CI, 24% to 54%), 50% (95% CI, 35% to 65%), 40% (95% CI, 25% to 56%), and 40% (95% CI, 25% to 56%), respectively. The odds ratio for ORR was 1.04 (P = 1.000) for arm 1 versus arm 2, 1.53 (P = .391) for arm 3 and versus arm 4, and 1.53 (P = .391) for arm 3 versus arm 5. The most common grade ≥ 3 adverse events were neutropenia, asthenia, anemia, thrombocytopenia, and hemoptysis. Of 161 available serum samples, a trend toward increased caspase-cleaved cytokeratin-18 was observed after dulanermin treatment in cycles 1 and 2. Among 84 patients evaluated for GalNT14 expression, there was a trend toward favorable progression-free survival and overall survival with dulanermin treatment in those with high GalNT14 expression.
The addition of dulanermin to PC and PCB did not improve outcomes in unselected patients with previously untreated advanced or recurrent NSCLC.
评估杜拉鲁肽联合紫杉醇和卡铂（PC）及贝伐珠单抗（PCB）作为晚期或复发性非小细胞肺癌（NSCLC）一线治疗的疗效和安全性。
鳞状 NSCLC 和/或 CNS 转移患者接受每 3 周单独的 PC 治疗（组 1）或接受 8 mg/kg 杜拉鲁肽治疗 5 天（组 2）。非鳞状 NSCLC 患者接受单独的 PCB 治疗（组 3）或接受 8 mg/kg 杜拉鲁肽治疗 5 天（组 4）或 2 天 20 mg/kg 杜拉鲁肽治疗（组 5）。主要终点为客观缓解率（ORR）。
共有 213 名患者被随机分配（组 1，n = 41；组 2，n = 39；组 3，n = 42；组 4，n = 40；组 5，n = 41）。组 1 至 5 的 ORR 分别为 39%（95%CI，24%至 56%）、38%（95%CI，24%至 54%）、50%（95%CI，35%至 65%）、40%（95%CI，25%至 56%）和 40%（95%CI，25%至 56%）。组 1 与组 2 的 ORR 比值比为 1.04（P = 1.000），组 3 与组 4 的 ORR 比值比为 1.53（P =.391），组 3 与组 5 的 ORR 比值比为 1.53（P =.391）。最常见的≥3 级不良事件为中性粒细胞减少症、乏力、贫血、血小板减少症和咯血。在 161 份可评估的血清样本中，在第 1 和第 2 周期中观察到杜拉鲁肽治疗后细胞角蛋白 18 切割半胱氨酸的趋势增加。在 84 名评估 GalNT14 表达的患者中，在高 GalNT14 表达的患者中，杜拉鲁肽治疗有改善无进展生存期和总生存期的趋势。
在未经选择的先前未经治疗的晚期或复发性 NSCLC 患者中，联合杜拉鲁肽的 PC 和 PCB 治疗并未改善结局。
