Bria Emilio, Gralla Richard J, Raftopoulos Harry, Cuppone Federica, Milella Michele, Sperduti Isabella, Carlini Paolo, Terzoli Edmondo, Cognetti Francesco, Giannarelli Diana
Department of Medical Oncology, Regina Elena National Cancer Institute, Roma, Italy.
Lung Cancer. 2009 Jan;63(1):50-7. doi: 10.1016/j.lungcan.2008.05.002. Epub 2008 Jun 18.
Several randomized trials investigating the benefit of adjuvant chemotherapy after surgery in non-small cell lung cancer (NSCLC) have provided conflicting results. With over 7000 patients included, we analyzed results of 13 reports over the past 10 years in which patients received either platinum-containing chemotherapy or not. The major endpoint was to assess the magnitude of the benefit of adjuvant chemotherapy in terms of the absolute benefit. All phase III randomized trials and meta-analyses published as peer-reviewed papers or as abstracts from 1994 to 2007 were eligible. A literature-based meta-analysis was performed; event-based overall- and disease-free survival (OS/DFS) and Relative Risks (RRs) with 95% confidence intervals (CIs) were derived. Magnitudes of benefit were evaluated with: absolute benefit and the number of patients treated for one patient to benefit. Seven sub-populations were examined. Combined effect estimation was computed with fixed- and random-effect models; a heterogeneity test was also applied. Twelve trials plus an individual patient meta-analysis (7334 patients) were gathered; the trials were designed to determine if cisplatin- or carboplatin-based chemotherapy improves survival over surgery. When data were pooled and plotted, significant differences in favor of chemotherapy were seen in OS in all seven sub-population, with a relative benefit of 7-12% and an absolute benefit ranging from 2.5% to 4.1%. A more significant trend for chemotherapy was found in DFS. No significant heterogeneity was observed for all outcomes and sub-populations. The absolute benefit of adjuvant chemotherapy remains essentially the same regardless of how data are screened. While significant differences are clearly found in this analysis, the small magnitude of benefit seen with this large population, especially when considering the number of patients needed for one to benefit, raises important issues when weighing risks and benefits of treatment for individual patients.
几项关于非小细胞肺癌（NSCLC）术后辅助化疗益处的随机试验得出了相互矛盾的结果。纳入了7000多名患者后，我们分析了过去10年中13份报告的结果，这些报告中的患者接受了含铂化疗或未接受含铂化疗。主要终点是从绝对获益的角度评估辅助化疗的获益程度。所有1994年至2007年发表为同行评审论文或摘要的III期随机试验和荟萃分析均符合条件。进行了基于文献的荟萃分析；得出了基于事件的总生存期和无病生存期（OS/DFS）以及95%置信区间（CI）的相对风险（RRs）。通过以下指标评估获益程度：绝对获益以及为使一名患者获益所需治疗的患者数量。检查了七个亚组。使用固定效应模型和随机效应模型计算合并效应估计值；还应用了异质性检验。收集了12项试验以及一项个体患者荟萃分析（7334名患者）；这些试验旨在确定基于顺铂或卡铂的化疗是否比手术能提高生存率。当汇总数据并绘图时，在所有七个亚组的总生存期方面均观察到有利于化疗的显著差异，相对获益为7% - 12%，绝对获益范围为2.5%至4.1%。在无病生存期方面发现了更显著的化疗趋势。对于所有结局和亚组均未观察到显著的异质性。无论如何筛选数据，辅助化疗的绝对获益基本保持不变。虽然在本分析中明确发现了显著差异，但在如此大量的人群中观察到的获益程度较小，尤其是考虑到使一名患者获益所需的患者数量时，这在权衡个体患者治疗的风险和获益时引发了重要问题。
