Abstract

BackgroundPemetrexed is widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). However, factors that can predict the benefits of pemetrexed therapy have not yet been defined.MethodsWe compared the clinical and molecule pathological characteristics of good and poor responders among a cohort of 1,848 non-squamous NSCLC patients who had received at least two cycles of pemetrexed therapy between November 2006 and February 2015. Among these cases, 92 good responders who were the top 5 % in terms of progression-free survival (PFS) and 222 poor responders who had progressive disease after only 2 cycles of therapy were selected for the analysis.ResultsThe median PFS of the good responders was 29.9 months (range; 20.9–90.0) and the median number of cycle was 37 (range; 18–129). Although 53.5 % of patients showed stable disease (SD), this response was sustained (median PFS in SD, 29.6 months). A never-smoking status was related to better survival outcome, whereas EGFR mutation, two or more metastatic sites, and intra-abdominal metastasis were each associated with a poor PFS. ALK translocation showed a tendency for a positive impact on response to pemetrexed, whereas metastatic lesion to liver, adrenal gland or bone showed a tendency for a negative impact despite not reaching our threshold for statistical significance.ConclusionsPredictive factors, such as smoking status, the status of genetic alteration and tumor burden, should be considered when administering pemetrexed therapy for non-squamous NSCLC.

Highlights

  • Pemetrexed is widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSCLC)

  • As pemetrexed was given in same cycle to those bottom 12 % of overall patients, a final cohort included 314 patients; the top 5 % (92 patients) and the bottom 12 % (222 patients) (Fig. 1)

  • We termed these patient groups as good responders and poor responders, respectively

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Summary

Introduction

Pemetrexed is widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). In Korea, 40.6 % of lung cancer patients have a metastatic lesion at the time of diagnosis [1]. Despite progress in the understanding of cancer biology and development of new therapeutic agents, the 5-year total survival rate for lung cancer remains 19.7 % overall and drops to 4.8 % in patients with a metastatic lesion at the time of diagnosis [1]. Pemetrexed has been widely used to treat patients with non-squamous non-small-cell lung cancer (NSCLC) because two separate phase III trials of this drug have reported prolonged survival in patients with non-squamous cell carcinoma compared with those with squamous cell carcinoma [2, 3]. Never-smoker, anaplastic lymphoma kinase (ALK) gene rearrangement, low tumor

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