Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin According to Thymidylate Synthase Expression in Nonsquamous Non-Small-Cell Lung Cancer: A Biomarker-Stratified Randomized Phase II Trial.

Journal Article (Journal Article)

PURPOSE: We investigated whether thymidylate synthase (TS) expression is a predictive marker for the clinical outcome of pemetrexed/cisplatin in patients with nonsquamous non-small-cell lung cancer. PATIENTS AND METHODS: Eligible patients were tested for TS expression by immunohistochemistry and stratified into either a TS-negative or a TS-positive group. After stratification, patients in each group were randomly assigned (1:1 ratio) to receive either pemetrexed/cisplatin or gemcitabine/cisplatin for a maximum of six cycles until disease progression. The primary end point was evaluation of the interaction between TS groups and treatment allocation for objective response rate. RESULTS: Of 321 enrolled patients with nonsquamous non-small-cell lung cancer, 315 received at least one dose of study chemotherapy and were analyzed. By investigator assessment, response rates were 47% for the pemetrexed/cisplatin arm and 21% for the gemcitabine/cisplatin arm in the TS-negative group and 40% and 39%, respectively, for the TS-positive group (interaction P = .0084). By independent reviewers, response rates of pemetrexed/cisplatin and gemcitabine/cisplatin were 39% and 21%, respectively, in the TS-negative group and 40% and 48% in the TS-positive group (interaction P = .0077). The median progression-free survival times for the pemetrexed/cisplatin and the gemcitabine/cisplatin arms were 6.4 and 5.5 months, respectively, in the TS-negative group and 5.9 and 5.3 months in the TS-positive group (interaction P = .07). CONCLUSION: With regard to response rate and progression-free survival, pemetrexed/cisplatin was superior to gemcitabine/cisplatin in the TS-negative group but not in the TS-positive group, indicative of TS expression as a potential predictive marker. Additional prospective studies involving larger cohorts are warranted to confirm the predictive role of TS expression.

Full Text

Duke Authors

Cited Authors

  • Sun, J-M; Ahn, JS; Jung, S-H; Sun, J; Ha, SY; Han, J; Park, K; Ahn, M-J

Published Date

  • August 1, 2015

Published In

Volume / Issue

  • 33 / 22

Start / End Page

  • 2450 - 2456

PubMed ID

  • 26124486

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2014.59.9324


  • eng

Conference Location

  • United States