Efficacy of Pemetrexed-based Chemotherapy in Comparison to Non-Pemetrexed-based Chemotherapy in Advanced, ALK+ Non-Small Cell Lung Cancer
Yonsei Medical Journal 2018³â 59±Ç 2È£ p.202 ~ p.210
Á¶Àç¹Î(Jo Jae-Min) - Seoul National University Bundang Hospital Department of Internal Medicine
±è¼¼Çö(Kim Se-Hyun) - Seoul National University Bundang Hospital Department of Internal Medicine
±èÀ¯Á¤(Kim Yu-Jung) - Seoul National University Bundang Hospital Department of Internal Medicine
ÀÌÁÖÇö(Lee Ju-Hyun) - Seoul National University Bundang Hospital Department of Internal Medicine
±è¹Ì¼Ò(Kim Mi-So) - Seoul National University Hospital Department of Internal Medicine
±è¹ü¼®(Keam Bhum-Suk) - Seoul National University Hospital Department of Internal Medicine
±èŹÎ(Kim Tae-MIn) - Seoul National University Hospital Department of Internal Medicine
±èµ¿¿Ï(Kim Dong-Wan) - Seoul National University Hospital Department of Internal Medicine
Çã´ë¼®(Heo Dae-Seog) - Seoul National University Hospital Department of Internal Medicine
Á¤ÁøÇà(Chung Jin-Haeng) - Seoul National University Bundang Hospital Department of Pathology
ÀüÀ±°æ(Jeon Yoon-Kyung) - Seoul National University Hospital Department of Pathology
ÀÌÁ¾¼®(Lee Jong-Seok) - Seoul National University Bundang Hospital Department of Internal Medicine
Abstract
Purpose: Previous retrospective studies suggest that anaplastic lymphoma kinase (ALK) mutation-positive (ALK+) non-small cell lung cancer (NSCLC) patients are sensitive to pemetrexed. To determine its efficacy, we retrospectively evaluated clinical outcomes of pemetrexed-based chemotherapy in patients with ALK+ NSCLC.
Materials and Methods: We identified 126 patients with advanced, ALK+ NSCLC who received first-line cytotoxic chemotherapy. We compared response, progression-free survival (PFS), and overall survival (OS) rates according to chemotherapy regimens. Furthermore, we evaluated intracranial time to tumor progression (TTP) and proportion of ALK+ cells as prognostic factors.
Results: Forty-eight patients received pemetrexed-based chemotherapy, while 78 received other regimens as first-line treatment. The pemetrexed-based chemotherapy group showed superior overall response (44.7% vs. 14.3%, p<0.001) and disease control (85.1% vs. 62.3%, p=0.008) rates. The pemetrexed-based chemotherapy group also exhibited longer PFS (6.6 months vs. 3.8 months, p<0.001); OS rates were not significantly different. The lack of exposure to second-generation ALK inhibitors and intracranial metastasis on initial diagnosis were independent negative prognostic factors of OS. Intracranial TTP was similar between the treatment groups (32.7 months vs. 35.7 months, p=0.733). Patients who harbored a greater number of ALK+ tumor cells (¡Ã70%) showed prolonged OS on univariate analysis (not reached vs. 44.8 months, p=0.041), but not on multivariate analysis (hazard ratio: 0.19, 95% confidence interval: 0.03?1.42; p=0.106).
Conclusion: Pemetrexed-based regimens may prolong PFS in patients with ALK+ NSCLC as a first-line treatment, but are not associated with prolonged OS. Exposure to second-generation ALK inhibitors may improve OS rates in patients with ALK+ NSCLC.
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Anaplastic lymphoma kinase, carcinoma, non-small-cell lung, pemetrexed
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A pemetrexed-based regimen may prolong A pemetrexed-based regimen may prolong progression-free survival (PFS), compared to other regimens, in patients with ALK+ NSCLC when administered as first-line palliative chemotherapy. However, pemetrexed-based regimens did not exhibit better intracranial activity and were not associated with improved OS., compared to other regimens, in patients with ALK+ NSCLC when administered as first-line palliative chemotherapy. However, pemetrexed-based regimens did not exhibit better intracranial activity and were not associated with improved OS.