Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Seoul National University Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Clin Lung Cancer. 2019 Jul;20(4):e442-e451. doi: 10.1016/j.cllc.2019.03.005. Epub 2019 Mar 29.
Leptomeningeal metastasis (LM), still an area of unmet need, has frequently been observed in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Because the antitumor efficacy of systemic cytotoxic agents against LM is unclear, we explored the role of pemetrexed in the treatment of patients with LM from EGFR-mutant NSCLC.
We retrospectively reviewed the medical records of patients with LM from EGFR-mutant NSCLC treated between 2006 and 2016. Post-LM survival was evaluated as well as clinical factors.
In our patient cohort with EGFR-mutant NSCLC (n = 631), 17.4% (n = 110) developed LM. Their median post-LM survival was 5.7 months (95% confidence interval, [CI], 0.0-12.0 months). Post-LM survival was significantly longer with pemetrexed use after LM (median, 13.7 months; 95% CI, 4.1-23.2 months) than without pemetrexed use after LM (median, 4.0 months; 95% CI, 2.2-5.7 months; P = .008). In the multivariate analyses, no pemetrexed use after LM (vs. use) and no EGFR tyrosine kinase inhibitor use after LM (vs. use) were independently associated with a poor post-LM survival with a hazard ratio of 3.1 (95% CI, 1.5-6.3; P = .002) and 3.0 (95% CI, 1.6-5.8; P = .001), respectively.
Pemetrexed use after LM was independently associated with a longer post-LM survival in patients with EGFR-mutant NSCLC with LM. Prospective studies are warranted to validate this finding.
脑膜转移（LM）仍然是一个未满足的需求领域，在 EGFR 突变型非小细胞肺癌（NSCLC）患者中经常观察到。由于全身细胞毒性药物对 LM 的抗肿瘤疗效尚不清楚，我们探讨了培美曲塞在治疗 EGFR 突变型 NSCLC 伴 LM 患者中的作用。
我们回顾性分析了 2006 年至 2016 年间 EGFR 突变型 NSCLC 伴 LM 患者的病历。评估了 LM 后的生存情况以及临床因素。
在我们的 EGFR 突变型 NSCLC 患者队列中（n=631），17.4%（n=110）发生 LM。他们的 LM 后中位生存时间为 5.7 个月（95%置信区间，[CI]，0.0-12.0 个月）。与 LM 后未使用培美曲塞（中位时间为 4.0 个月；95%CI，2.2-5.7 个月）相比，LM 后使用培美曲塞（中位时间为 13.7 个月；95%CI，4.1-23.2 个月）的 LM 后生存时间显著延长（P=0.008）。多变量分析显示，LM 后未使用培美曲塞（与使用相比）和 LM 后未使用 EGFR 酪氨酸激酶抑制剂（与使用相比）与 LM 后预后不良独立相关，风险比分别为 3.1（95%CI，1.5-6.3；P=0.002）和 3.0（95%CI，1.6-5.8；P=0.001）。
LM 后使用培美曲塞与 EGFR 突变型 NSCLC 伴 LM 患者的 LM 后生存时间延长独立相关。需要前瞻性研究来验证这一发现。
