Efficacy of Pemetrexed-based Chemotherapy in Comparison to Non-Pemetrexed-based Chemotherapy in Advanced, ALK+ Non-Small Cell Lung Cancer.
10.3349/ymj.2018.59.2.202
- Author:
Jaemin JO
1
;
Se Hyun KIM
;
Yu Jung KIM
;
Juhyun LEE
;
Miso KIM
;
Bhumsuk KEAM
;
Tae Min KIM
;
Dong Wan KIM
;
Dae Seog HEO
;
Jin Haeng CHUNG
;
Yoon Kyung JEON
;
Jong Seok LEE
Author Information
1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. jslee@snubh.org
- Publication Type:Original Article
- Keywords:
Anaplastic lymphoma kinase;
carcinoma;
non-small-cell lung;
pemetrexed
- MeSH:
Adult;
Aged;
Antineoplastic Agents/*therapeutic use;
Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology/mortality;
Disease-Free Survival;
Female;
Humans;
Lung Neoplasms/*drug therapy/enzymology/mortality;
Male;
Middle Aged;
Mutation;
Pemetrexed/*therapeutic use;
Receptor Protein-Tyrosine Kinases/genetics;
Retrospective Studies;
Survival Rate;
Treatment Outcome
- From:Yonsei Medical Journal
2018;59(2):202-210
- CountryRepublic of Korea
- Language:English
-
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.
