Yonsei Med J.  2018 Mar;59(2):202-210. 10.3349/ymj.2018.59.2.202.

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

• Jo J
• Kim SH
• Kim YJ
• Lee J
• Kim M
• Keam B
• Kim TM
• Kim DW
• Heo DS
• Chung JH
• Jeon YK
• Lee JS

• KMID: 2418782
• DOI: http://doi.org/10.3349/ymj.2018.59.2.202

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.

Keyword

Anaplastic lymphoma kinase; carcinoma; non-small-cell lung; pemetrexed

MeSH Terms

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
Antineoplastic Agents
Pemetrexed
Receptor Protein-Tyrosine Kinases

Figure

• 

  Fig. 1 PFS according to first-line cytotoxic treatment. PFS, progression-free survival; mPFS, median PFS; mo, months.

• 

  Fig. 2 OS according to first-line cytotoxic treatment (A), pemetrexed exposure (B), second-generation ALKi exposure (C), and ALK+ tumor cell proportion (D). OS, overall survival; ALK, anaplastic lymphoma kinase; FISH, fluorescence in situ hybridization; mOS, median overall survival; mo, months; ALKi, anaplastic lymphoma kinase inhibitor.

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