培美曲塞联合卡铂可显著提高非小细胞肺癌患者总体生存期

一项III期临床试验表明：培美曲塞（力比泰）和卡铂可显著提高晚期、体力状况差的非小细胞肺癌（NSCLC）患者的总生存期。

体力状况2分的晚期NSCLC患者尚无统一的标准治疗。一项研究的亚组分析显示卡铂联合培美曲塞较培美曲塞单药显著改善患者的1年生存率；另外一项试验表明健择联合卡铂治疗晚期、PS 2分NSCLC患者可较健择单药显著提高无进展生存期（PFS）和客观缓解率（ORR），生存有延长趋势，但因试验过早终止未得出统计学差异；另一项比较培美曲塞联合或不联合卡铂的试验证明联合治疗可显著提高70岁及以上老年晚期NSCLC患者的生存期。

基于这几项研究的有利结果，巴西的研究者在PS 2分的晚期NSCLC患者中进行了一项前瞻性、III期、多中心、随机临床研究。研究者入组了III/IV期、PS 2分的NSCLC患者205例，中位年龄65岁，1/3以上的患者为70岁及以上。95%的患者为IV期，一半以上的患者体重减轻5%或以上。大约3/4的患者正在或曾经为吸烟者。入组患者随机分配入培美曲塞单药或联合卡铂组行一线治疗。试验的主要终点为总生存期。

研究人群试验中位随访6.1个月后终止。联合治疗组有3.5个月的总生存获益（9.1月和5.6月），可转化为降低43%的风险比（P=0.001）。6个月生存率培美曲塞单药组为50%，联合治疗组为65%，12个月生存率则分别为18%和43%。联合治疗组的中位无进展生存期几乎是单药组的两倍（5.9月vs 3.0月，HR 0.46， P<0.001)，联合治疗组的客观缓解率则超过单药组的两倍(24.0% vs 10.5%，P<0.029)。另外，联合治疗组中60.8%的患者疾病稳定，而培美曲塞单药治疗组仅有42.6%。

预先设定的亚组分析显示：联合治疗在不同的吸烟状况和患者年龄亚组均有一致的获益。联合治疗组最常见的3/4级毒性为贫血(11.7%)，培美曲塞单药治疗组为呼吸困难(10.8%)。关于这些毒性及其他毒性的发生率，治疗组与对照组无显著差异。在ASCO年会上，医学博士Rogerio Lilenbaum报告说该联合方案可作为晚期体力状况评分2分的NSCLC患者的新的标准方案。

韦斯顿佛罗里达州克利夫兰诊所的Lilenbaum说：“这个试验证明低毒性的两药方案，如培美曲塞和卡铂，能提高PS 2分患者的反应率及生存期，是PS 2分患者的一种选择。鉴于该数据显示出明显获益，为了使其马上应用于临床，我们强烈建议协作组更新指南。”

摘要号：7506

题目：A randomized phase III trial of single-agent pemetrexed (P) versus carboplatin and pemetrexed (CP) in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2.

单药培美曲塞(P)对比卡铂联合培美曲塞(CP)治疗PS评分为2的晚期非小细胞肺癌(NSCLC)的III期随机研究

摘要：

Background: No standard of care exists for patients with advanced NSCLC and PS 2 and clinical practice ranges from supportive care to combination chemotherapy.

Methods: In a Brazilian multicenter phase III randomized trial, advanced NSCLC patients, with any histology at first, amended to non-squamous only, PS 2, no prior chemotherapy, and adequate organ function, were randomized to P alone (500 mg/m2) or CP (AUC 5 + same P) administered every 3 weeks for 4 cycles. Stratification factors included stage (IIIB vs. IV); age (≥70 vs. <70); and weight loss (≥5 kg vs. <5kg). The primary endpoint was overall survival and the study was powered to demonstrate an improvement in median survival from 2.9 to 4.3 months based on a prior CALGB trial.

Results: A total of 217 patients were enrolled from 8 centers in Brazil and 1 in the US from April 2008 to July 2011. Twelve patients were ineligible and excluded. The 2 arms (P=102; CP=103) were balanced for patient characteristics. 14 patients had squamous and another 12 had unknown histology. The response rates were P = 10% and CP = 24% (p=0.019). In the ITT population, the median PFS was P = 3.0 mo and CP = 5.9 mo (HR=0.46, 95% CI 0.34; 0.63, p<0.001) and median OS was P = 5.6 mo vs. CP = 9.1 mo (HR=0.57, 95% CI 0.41; 0.79, p=0.001). 1-year survival rates were 22% and 39% respectively. Similar results were seen when squamous patients were excluded from the analysis. Grade ?? anemia (5.5%; 12%) and neutropenia (2.8%; 5.6%) were more frequent in CP. There were 4 treatment-related deaths in the CP arm. 30% of patients in each arm received 2nd line therapy

Conclusions: Combination chemotherapy with CP significantly improves survival, with acceptable safety, in eligible patients with advanced NSCLC and PS 2, and represents a new standard.

编辑: xy 作者:丁香园通讯员

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