Asan Medical Center, Seoul, Republic of Korea.
Eur J Cancer. 2013 Oct;49(15):3111-21. doi: 10.1016/j.ejca.2013.06.035. Epub 2013 Jul 24.
This randomised controlled phase 2 study compared pemetrexed and erlotinib in combination with either agent alone in terms of efficacy and safety as second-line treatment in a clinically selected population of never-smokers with non-squamous non-small cell lung cancer (NSCLC).
Patients who had failed only one prior chemotherapy regimen and had Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2 were randomised to either: pemetrexed 500 mg/m(2) on day 1 plus erlotinib 150 mg daily on days 2-14; erlotinib 150 mg daily; or pemetrexed 500 mg/m(2) on day 1 of a 21-day cycle until discontinuation criteria were met. The primary endpoint, progression-free survival (PFS), was analysed using a multivariate Cox model. Firstly, a global comparison across the three arms was performed. If the global null hypothesis was rejected at a two-sided 0.2 significance level, pairwise comparisons of pemetrexed-erlotinib versus erlotinib or pemetrexed were then conducted using the same model. Statistical significance was claimed only if both global and pairwise null hypotheses were rejected at a two-sided 0.05 significance level.
A total of 240 patients (male, 35%; East Asian, 55%; ECOG PS 0-1, 93%) were included. A statistically significant difference in PFS was found across the three arms (global p=0.003), with pemetrexed-erlotinib significantly better than either single agent: HR=0.57, 95% confidence interval (CI): 0.40-0.81, p=0.002 versus erlotinib; HR=0.58, 95% CI: 0.39-0.85, p=0.005 versus pemetrexed. Median PFS (95% CI) was 7.4 (4.4, 12.9) months in pemetrexed-erlotinib, 3.8 (2.7, 6.3) months in erlotinib and 4.4 (3.0, 6.0) months in pemetrexed. Safety analyses showed a higher incidence of drug-related grade 3/4 toxicity in pemetrexed-erlotinib (60.0%) than in pemetrexed (28.9%) or erlotinib (12.0%); the majority being neutropenia, anaemia, rash and diarrhoea.
Pemetrexed-erlotinib significantly improved PFS compared to either drug alone in this clinically selected population. The combination had more toxicity, but was clinically manageable.
这项随机对照的 2 期研究比较了培美曲塞和厄洛替尼联合与单独使用这两种药物作为二线治疗在临床选择的从不吸烟的非鳞状非小细胞肺癌（NSCLC）患者中的疗效和安全性。
仅在前一种化疗方案失败且东部合作肿瘤学组（ECOG）表现状态（PS）≤2 的患者中，随机分为以下三组：培美曲塞 500mg/m²，第 1 天；厄洛替尼 150mg，每日 1 次，第 2-14 天；厄洛替尼 150mg，每日 1 次；或培美曲塞 500mg/m²，每 21 天周期 1 天，直至达到停药标准。无进展生存期（PFS）是主要终点，采用多变量 Cox 模型进行分析。首先，对三组进行了全局比较。如果双侧 0.2 显著性水平的总体零假设被拒绝，则使用相同的模型对培美曲塞-厄洛替尼与厄洛替尼或培美曲塞进行两两比较。仅当双侧 0.05 显著性水平的总体和两两零假设均被拒绝时，才声称具有统计学意义。
共纳入 240 例患者（男性，35%；东亚裔，55%；ECOG PS 0-1，93%）。三组之间 PFS 存在统计学差异（全局 p=0.003），培美曲塞-厄洛替尼显著优于任一单药：HR=0.57，95%置信区间（CI）：0.40-0.81，p=0.002 与厄洛替尼相比；HR=0.58，95%CI：0.39-0.85，p=0.005 与培美曲塞相比。培美曲塞-厄洛替尼的中位 PFS（95%CI）为 7.4（4.4，12.9）个月，厄洛替尼为 3.8（2.7，6.3）个月，培美曲塞为 4.4（3.0，6.0）个月。安全性分析显示，培美曲塞-厄洛替尼（60.0%）的药物相关 3/4 级毒性发生率高于培美曲塞（28.9%）或厄洛替尼（12.0%）；大多数是中性粒细胞减少症、贫血、皮疹和腹泻。
在这一临床选择的人群中，培美曲塞-厄洛替尼与任一药物单独使用相比，显著改善了 PFS。该联合用药具有更高的毒性，但在临床治疗上是可控的。
