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J Clin Oncol. 2015 Aug 1;33(22):2450-6. doi: 10.1200/JCO.2014.59.9324. Epub 2015 Jun 29.

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.

Author information

1
Jong-Mu Sun, Jin Seok Ahn, Sin-Ho Jung, Jiyu Sun, Sang Yun Ha, Joungho Han, Keunchil Park, and Myung-Ju Ahn, Sungkyunkwan University School of Medicine, Seoul, Korea; and Sin-Ho Jung, Duke University, Durham, NC.
2
Jong-Mu Sun, Jin Seok Ahn, Sin-Ho Jung, Jiyu Sun, Sang Yun Ha, Joungho Han, Keunchil Park, and Myung-Ju Ahn, Sungkyunkwan University School of Medicine, Seoul, Korea; and Sin-Ho Jung, Duke University, Durham, NC. silkahn@skku.edu.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01401192.

PMID:
26124486
DOI:
10.1200/JCO.2014.59.9324
[Indexed for MEDLINE]

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