2015-05-28 00:00:00来源：医脉通阅读：28次
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2015年ASCO年会将于5月29日--6月2日在美国芝加哥召开，5月31日上午的非小细胞肺癌（NSCLC）口头报告专场，将公布WJOG5208L的结果，这是一项对比奈达铂+多西他赛和顺铂+多西他赛治疗晚期或复发性肺鳞状细胞癌（SqLC）的III期随机对照研究。摘要结果表明，奈达铂+多西他赛方案相比顺铂+多西他赛方案有明显更长的OS。
背景：奈达铂（N）是一种二代铂类化合物，比顺铂（C）有更低的恶心/呕吐发生率和肾脏毒性。既往II期研究发现，奈达铂+多西他赛（ND）治疗SqLC患者有效，且毒性可接受。
方法：研究纳入标准为，病理学证实SqLC，IIIB/IV期或术后复发，年龄20-74岁，ECOG PS 0-1。根据分期、性别和机构将患者1:1随机分配到ND（N，100mg/m2；D，60mg/m2，iv，q3w，达6个周期）或者C+D（C，80mg/m2；D，60mg/m2，iv, q3w,达6个周期）治疗。主要终点是总生存期（OS），次要终点包括无进展生存期（PFS），缓解率（RR）和不良事件（AEs）。目标样本量为350，达到90%的统计学效能以检测出0.71的HR，单侧I型错误为0.05。
结果：从2009年7月到2012年7月，355例患者被纳入研究。其中349名患者进行疗效分析（ND，177；CD，172），患者基线特征在组间有良好的平衡。结果发现ND组有明显更长的OS（p=0.037），ND组和CD组的中位OS分别为13.6和11.4个月，OS的HR为0.81（90%CI，0.67-0.98）。ND组同样有更长的PFS（p=0.050），ND组和CD组的中位PFS分别为4.9和4.5个月，HR为0.83（0.69-1.00）。ND组和CD组的RR分别为54.5%和52.9%(p=0.829)。
CD组更常见的3级及以上的不良事件如下：恶心（4.0% vs 14.3%），乏力（3.4% vs 10.9%），低钠血症（13.6% vs 30.3%）和低钾血症（2.3% vs 8.6%）。ND组更常见3级及以上的不良事件为中性粒细胞减少（82.5% vs 70.3%）和血小板减少（9.0% vs 0.0%）。两组间3级及以上的发热性中性粒细胞减少的发生率并无差异（13.6% vs 15.4%）。ND和CD组分别有4例和3例治疗相关的死亡事件。
结论：ND方案相比CD方案有明显更长的OS，两种方案的毒性表现不同。对于晚期或复发性SqLC患者，ND方案将被考虑作为一种新的标准治疗方案。临床试验信息：: UMIN000002015
会议专题》》》2015年ASCO年会专题报道
阅读摘要原文
Randomized phase III study of nedaplatin (N) plus docetaxel (D) versus cisplatin (C) plus D for advanced or relapsed squamous cell carcinoma of the lung (SqLC): WJOG5208L.（Abstract No:8004）
Author(s): Takehito Shukuya, Takeharu Yamanaka, Takashi Seto, Haruko Daga, et al
Type: Oral Abstract Session
Background: N is a second-generation platinum compound with lower nausea/vomiting and nephrotoxicity than C. N plus D (ND) showed a promising efficacy with acceptable toxicity for advanced SqLC in the previous phase II study.
Methods: Eligible patients (pts) were those with pathologically proven SqLC with stage IIIB/IV or postoperative recurrence, aged 20-74 and ECOG PS 0-1. Pts were randomized 1:1 to ND (N 100 mg/m2 and D 60mg/m2 intravenous, q3w, up to 6 cycles) or C plus D (CD) (C 80 mg/m2 and D 60mg/m2 intravenous, q3w, up to 6 cycles) according to stage, gender and institution. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate (RR) and adverse events (AEs). Target sample size of 350 provided 90% statistical power to detect a hazard ratio of 0.71 with one-sided type I error of 0.05.
Results: Between July 2009 and July 2012, 355 pts were randomized. Of 349 for efficacy analysis (ND 177; CD 172), baseline characteristics were well-balanced between two arms. ND had a significantly longer OS (p = 0.037, one-sided stratified log-rank test). The OS HR was 0.81 (90%CI, 0.67-0.98) with a median OS of 13.6 months [m] for ND and 11.4 for CD. ND had a longer PFS (p = 0.050) with a HR of 0.83 (0.69-1.00) and a median PFS of 4.9 m in ND and 4.5 in CD. RR was 54.5% in ND vs 52.9% in CD (p = 0.829). Grade 3 or higher AEs of nausea (4.0% vs 14.3%), fatigue (3.4% vs 10.9%), hyponatremia (13.6% vs 30.3%) and hypokalemia (2.3% vs 8.6%) are more frequent in CD. Grade 3 or higher AEs of neutrophils (82.5% vs 70.3%) and platelets (9.0% vs 0.0%) are more frequent in ND, but there was no difference in grade 3 or higher febrile neutropenia (13.6% vs 15.4%). Treatment related deaths occurred in 4 and 3 pts in ND and CD, respectively.
Conclusions: ND showed a significantly longer OS as compared to CD with different toxicity profile. ND will be considered as a new standard treatment for advanced or relapsed SqLC. Clinical trial information: UMIN000002015