Cancer Res Treat.  2015 Oct;47(4):630-637. 10.4143/crt.2014.244.

Pemetrexed Singlet Versus Nonpemetrexed-Based Platinum Doublet as Second-Line Chemotherapy after First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Failure in Non-small Cell Lung Cancer Patients with EGFR Mutations

Affiliations
  • 1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. bhumsuk@snu.ac.kr
  • 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 3Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.

Abstract

PURPOSE
Platinum-based doublet chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC); however, the role of a platinum-based doublet as second-line therapy after failure of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC patients has not yet been elucidated. The purpose of this study was to compare the clinical efficacy of pemetrexed versus a platinum-based doublet as second-line therapy after failure of EGFR TKI used as first-line therapy for NSCLC patients with EGFR mutations.
MATERIALS AND METHODS
We designed a multicenter retrospective cohort study of 314 NSCLC patients with EGFR mutations who received an EGFR TKI as first-line palliative chemotherapy. Our analysis included 83 patients who failed EGFR TKI therapy and received second-line cytotoxic chemotherapy.
RESULTS
Forty-six patients were treated using a platinum-based doublet and 37 patients were treated using singlet pemetrexed. The overall response rates of patients receiving a platinum-based doublet and patients receiving pemetrexed were17.4% and 32.4%, respectively (p=0.111). The median progression-free survival (PFS) of patients receiving pemetrexed was significantly longer than that of patients receiving a platinum-based doublet (4.2 months vs. 2.7 months, respectively; p=0.008). The hazard ratio was 0.54 (95% confidence interval, 0.34 to 0.86; p=0.009).
CONCLUSION
Our retrospective analysis found that second-line pemetrexed singlet therapy provided significantly prolonged PFS compared to second-line platinum-based doublet chemotherapy for NSCLC patients with EGFR mutations who failed first-line EGFR TKI. Conduct of prospective studies for confirmation of our results is warranted.

Keyword

Platinum; Pemetrexed; Non-small-cell lung carcinoma; Epidermal growth factor receptor

MeSH Terms

Carcinoma, Non-Small-Cell Lung*
Cohort Studies
Disease-Free Survival
Drug Therapy*
Epidermal Growth Factor*
Humans
Phosphotransferases*
Platinum*
Prospective Studies
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor*
Retrospective Studies
Epidermal Growth Factor
Phosphotransferases
Platinum
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor

Figure

  • Fig. 1. Flow chart for selection of study patients. EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.

  • Fig. 2. FKaplan-Meier curves for progression-free survival (PFS) from the start of second-line chemotherapy (A), for overall survival (OS) from the start of second-line chemotherapy (B), for PFS from the start of first-line tyrosine kinase inhibitor (C), and for OS from the start of first-line tyrosine kinase inhibitor (D).


Reference

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