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Efficacy of Pemetrexed-based Chemotherapy in Comparison to Non-Pemetrexed-based Chemotherapy in Advanced, ALK+ Non-Small Cell Lung Cancer

Yonsei Medical Journal
2018년 59권 2호 p.202 ~ p.210
조재민 ( Jo Jae-Min ) - Seoul National University Bundang Hospital Department of Internal Medicine

김세현 ( Kim Se-Hyun ) - Seoul National University Bundang Hospital Department of Internal Medicine
김유정 ( Kim Yu-Jung ) - Seoul National University Bundang Hospital Department of Internal Medicine
이주현 ( Lee Ju-Hyun ) - Seoul National University Bundang Hospital Department of Internal Medicine
김미소 ( Kim Mi-So ) - Seoul National University Hospital Department of Internal Medicine
김범석 ( Keam Bhum-Suk ) - Seoul National University Hospital Department of Internal Medicine
김태민 ( Kim Tae-MIn ) - Seoul National University Hospital Department of Internal Medicine
김동완 ( Kim Dong-Wan ) - Seoul National University Hospital Department of Internal Medicine
허대석 ( Heo Dae-Seog ) - Seoul National University Hospital Department of Internal Medicine
정진행 ( Chung Jin-Haeng ) - Seoul National University Bundang Hospital Department of Pathology
전윤경 ( Jeon Yoon-Kyung ) - Seoul National University Hospital Department of Pathology
이종석 ( 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 (≥70%) 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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