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Pemetrexed-based chemotherapy in advanced lung adenocarcinoma patients with different EGFR genotypes

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Tumor Biology

Abstract

Advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) activating mutations usually are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs), but whether EGFR-mutant lung adenocarcinoma is also responsive to pemetrexed-based chemotherapy remains controversial. We conducted a retrospective study to evaluate the efficacy and outcome of pemetrexed-based chemotherapy in advanced lung adenocarcinoma patients with different EGFR mutation statuses. Sixty-nine EGFR-mutant and 89 wild-type patients with advanced lung adenocarcinoma were enrolled. They all had received pemetrexed-based treatments. Chemotherapy objective response rate (ORR), median progression-free survival (mPFS), and thymidylate synthase (TS) expression levels of EGFR-mutant patients were compared with those of EGFR-wild-type patients. For the EGFR-mutant patients treated with first-line platinum/pemetrexed combinations, the ORR was significantly higher than that of the wild-type patients treated with similar regimens (43 vs. 21 %, p = 0.039). Nonetheless, for the patients treated with pemetrexed monotherapy, the difference in ORR was not significant between patients with EGFR mutations and those with wild-type EGFR in any line of treatments (in the first-line setting 20 vs. 13 %, p = 0.715; in the second-/third-line setting 13 vs. 8 %, p = 0.655). On the other hand, the mPFS for the EGFR-mutant patients treated with first-line combinations was also obviously prolonged (8.3 vs. 6.7 months, p = 0.004). However, among the patients receiving second-line platinum/pemetrexed combinations or any line of single-agent pemetrexed, there was no difference in PFS between EGFR-mutant and wild-type patients. Our results indicated that the efficacies and outcomes of pemetrexed treatment in advanced lung adenocarcinoma patients with EGFR activating mutations were similar to those in patients with EGFR-wild-type genotype, except in the setting of first-line platinum/pemetrexed combination chemotherapy.

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Acknowledgments

This work was supported by the National Basic Research Program of China (973 program, No. 2012CB9333004) and Tianjin Science and Technology Project (Crucial Special Anticancer Program, No.12ZCDZSY15600).

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Authors and Affiliations

  1. Department of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Xiangli Jiang, Jiuqin Lu & Kai Li

  2. Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Bo Yang & Zhongli Zhan

  3. Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin, 300060, China

    Xiubao Ren

  4. Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin, 300060, China

    Xiangli Jiang & Xiubao Ren

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  1. Xiangli Jiang
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Correspondence to Kai Li or Xiubao Ren.

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Xiangli Jiang and Bo Yang contribute equally to this paper.

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Jiang, X., Yang, B., Lu, J. et al. Pemetrexed-based chemotherapy in advanced lung adenocarcinoma patients with different EGFR genotypes. Tumor Biol. 36, 861–869 (2015). https://doi.org/10.1007/s13277-014-2692-4

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  • DOI: https://doi.org/10.1007/s13277-014-2692-4

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