Jong-Mu Sun1, Jin Seok Ahn1, Sin-Ho Jung1, Jiyu Sun1, Sang Yun Ha1, Joungho Han1, Keunchil Park1, Myung-Ju Ahn2. 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.
RCT Entities:
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.
Authors: Stephen J Bagley; Steven Vitale; Suhong Zhang; Charu Aggarwal; Tracey L Evans; Evan W Alley; Roger B Cohen; Corey J Langer; Ian A Blair; Anil Vachani; Alexander S Whitehead Journal: Clin Lung Cancer Date: 2016-10-26 Impact factor: 4.785
Authors: E Giovannetti; P A Zucali; Y G Assaraf; N Funel; M Gemelli; M Stark; E Thunnissen; Z Hou; I B Muller; E A Struys; M Perrino; G Jansen; L H Matherly; G J Peters Journal: Ann Oncol Date: 2017-11-01 Impact factor: 32.976