1242P - Thymidylate synthase expression can guide treatment selection for advanced non-small cell lung cancer patients

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Presenter Tetsuo Shimizu
Authors T. Shimizu1, Y. Nakanishi2, Y. Nakagawa1, I. Tsujino1, N. Takahashi1, S. Hashimoto1, N. Nemoto2
  • 1Respiratory Medicine, Nihon University School of Medicine, 173-8610 - Tokyo/JP
  • 2Pathology, Nihon University School of Medicine, Tokyo/JP

Abstract

Background

Combination cisplatin plus pemetrexed (PMT) and carboplatin plus paclitaxel with bevacizumab are standard first-line chemotherapies for advanced non-small cell lung cancer (NSCLC). However, it is unclear whether a PMT-based regimen or taxane-based regimen should be selected for patients with advanced NSCLC. Thymidylate synthase (TS) is an important enzyme in DNA synthesis and influences sensitivity to several anti-cancer drugs. The purpose of this study is to determine whether TS expression affects the therapeutic efficacy of PMT or taxane.

Methods

Participants were 94 patients with advanced NSCLC treated with PMT or taxane. Samples were obtained by tumor biopsy prior to treatment. Cancer cells were isolated from formalin-fixed paraffin-embedded tissue using laser microdissection, and mRNA levels were analyzed using real-time reverse transcription polymerase chain reaction. Protein expression was evaluated using immunohistochemistry. The association between TS expression and therapeutic efficacy was evaluated.

Results

Fifty patients received PMT, 51 patients received taxane, and 7 patients received both regimens. TS expression was significantly lower in PMT responders compared with PMT non-responders (p = 0.0142), but significantly higher in taxane responders compared with taxane non-responders (p = 0.0486). In patients with low expression of TS, progression-free survival (PFS) was prolonged for the PMT-based regimen compared with the taxane-based regimen (21.9 versus 18.7 weeks, p = 0.5661). Conversely, in patients with high expression of TS, PFS for the taxane-based regimen was superior to that for the PMT-based regimen (19.9 versus 13.3 weeks, p = 0.2433).

Conclusion

The PMT-based regimen afforded better outcome in patients with low expression of TS, whereas the taxane-based regimen was better in patients with high expression of TS. Thus, TS expression could be a useful biomarker for treatment selection in NSCLC patients receiving PMT- or taxane-based chemotherapy.

Disclosure

All authors have declared no conflicts of interest.