Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN 46285, USA.
Clin Lung Cancer. 2012 Jan;13(1):24-30. doi: 10.1016/j.cllc.2011.05.007. Epub 2011 Aug 10.
Symptomatic brain metastases (BM) frequently occurs after initial treatment of non-small-cell lung cancer (NSCLC). Therefore, 2 large randomized trials that involved pemetrexed were retrospectively analyzed to determine the pattern of symptomatic relapse in the brain and to gauge if pemetrexed could influence the incidence.
Two large phase III studies of pemetrexed in advanced NSCLC were included. One study compared pemetrexed with docetaxel in previously treated patients (n = 571); the other study tested cisplatin plus pemetrexed vs. cisplatin plus gemcitabine in chemotherapy-naive patients with advanced NSCLC (n = 1725). Patients with known BM at study entry were excluded from this analysis. Each study was analyzed separately, then jointly to determine the rate of BM reported as the only site of progressive disease by treatment group and histology. Logistic regression was used to obtain an odds ratio for the treatment effect on the overall occurrence of BM while controlling for potential confounding factors.
Overall, 71.5% of patients in pemetrexed-containing arms (819 of 1145), and 68.2% of patients in non-pemetrexed-containing arms (785 of 1151) experienced progressive disease. BM recurrence rates were 3.2% (95% confidence interval [CI], 2.1%-4.6%) in the pemetrexed-containing arms vs. 6.6% (95% CI, 5.0%-8.6%) in the non-pemetrexed-containing arms (P = .002). The odds ratio for BM recurrence associated with exposure to pemetrexed was 0.49 (95% CI, 0.32-0.76; P = .001). The beneficial effect of pemetrexed on BM was confined to patients with nonsquamous NSCLC.
Patients with advanced nonsquamous NSCLC treated with pemetrexed either in first-line or second-line therapy may reduce the risk of developing BM as the first site of progressive disease. This retrospective analysis is limited due to the lack of baseline and periodic brain scans, and it reflects symptomatic BM only. Regardless, these findings suggest a potential beneficial effect of pemetrexed-based treatments on the control of BM.
非小细胞肺癌（NSCLC）初始治疗后常出现有症状的脑转移（BM）。因此，回顾性分析了两项包含培美曲塞的大型随机试验，以确定脑内有症状复发的模式，并评估培美曲塞是否会影响发生率。
纳入两项培美曲塞治疗晚期 NSCLC 的大型 III 期研究。一项研究比较了培美曲塞与多西他赛在既往治疗患者中的疗效（n=571）；另一项研究比较了顺铂联合培美曲塞与顺铂联合吉西他滨在初治晚期 NSCLC 患者中的疗效（n=1725）。本分析排除了研究入组时已知有 BM 的患者。分别对每个研究进行分析，然后联合分析以确定按治疗组和组织学报告的仅作为进展性疾病的 BM 发生率。使用逻辑回归在控制潜在混杂因素的情况下获得治疗对总体 BM 发生的优势比。
总体而言，培美曲塞组中 71.5%的患者（1145 例中的 819 例）和非培美曲塞组中 68.2%的患者（1151 例中的 785 例）出现疾病进展。培美曲塞组的 BM 复发率为 3.2%（95%置信区间[CI]，2.1%-4.6%），而非培美曲塞组为 6.6%（95% CI，5.0%-8.6%）（P=0.002）。与培美曲塞暴露相关的 BM 复发优势比为 0.49（95% CI，0.32-0.76；P=0.001）。培美曲塞对 BM 的有益作用仅限于非鳞状 NSCLC 患者。
接受培美曲塞一线或二线治疗的晚期非鳞状 NSCLC 患者可能会降低作为首发进展性疾病的 BM 发生风险。由于缺乏基线和定期的脑部扫描，该回顾性分析存在局限性，并且仅反映了有症状的 BM。尽管如此，这些发现表明培美曲塞治疗可能对控制 BM 有潜在的有益作用。
