Skip to main content

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.

Publication ,  Journal Article
Sun, J-M; Ahn, JS; Jung, S-H; Sun, J; Ha, SY; Han, J; Park, K; Ahn, M-J
Published in: J Clin Oncol
August 1, 2015

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

August 1, 2015

Volume

33

Issue

22

Start / End Page

2450 / 2456

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thymidylate Synthase
  • Predictive Value of Tests
  • Pemetrexed
  • Oncology & Carcinogenesis
  • Molecular Targeted Therapy
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sun, J.-M., Ahn, J. S., Jung, S.-H., Sun, J., Ha, S. Y., Han, J., … Ahn, M.-J. (2015). 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. J Clin Oncol, 33(22), 2450–2456. https://doi.org/10.1200/JCO.2014.59.9324
Sun, Jong-Mu, Jin Seok Ahn, Sin-Ho Jung, Jiyu Sun, Sang Yun Ha, Joungho Han, Keunchil Park, and Myung-Ju Ahn. “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.J Clin Oncol 33, no. 22 (August 1, 2015): 2450–56. https://doi.org/10.1200/JCO.2014.59.9324.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

August 1, 2015

Volume

33

Issue

22

Start / End Page

2450 / 2456

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thymidylate Synthase
  • Predictive Value of Tests
  • Pemetrexed
  • Oncology & Carcinogenesis
  • Molecular Targeted Therapy
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Humans