title: Efficacy and safety of pemetrexed/cisplatin versus gemcitabine/cisplatin as first-line treatment in Chinese patients with advanced nonsquamous non-small cell lung cancer.
abstract: OBJECTIVE
  Retrospective subgroup analysis in JMDB study indicates that the between-arm differences in overall survival (OS) in the East Asian subgroup were consistent with those observed in the entire JMDB study population. This bridging study (JMIL) further evaluated the efficacy and safety of first-line pemetrexed/cisplatin (PC) versus gemcitabine/cisplatin (GC) in Chinese patients with nonsquamous non-small cell lung cancer (NSCLC). The primary endpoint of this local registration trial was designed to compare OS in the combined dataset, consisting of Chinese patients in JMIL and 1252 nonsquamous patients in JMDB.
  
  
  METHODS
  Chinese patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned (1:1) to 6 cycles maximum (21 days/cycle) of pemetrexed 500mg/m(2)+cisplatin 75mg/m(2) (day 1), or gemcitabine 1250mg/m(2) (days 1 and 8)+cisplatin 75mg/m(2) (day 1).
  
  
  RESULTS
  In JMIL, 256 Chinese patients were randomized (PC, n=126; GC, n=130). Patient baseline characteristics were balanced between treatment arms. In the combined dataset, PC was superior to GC in prolonging OS, with adjusted hazard ratio (HR) of 0.87 (95% CI: 0.77-0.98, p=0.023) and median OS of 11.76 versus 10.94 months. In the JMIL-only population, no significant OS difference observed between treatment arms (adjusted HR=1.03 [95% CI: 0.77-1.39, p=0.822]; unadjusted HR=0.996 [95% CI: 0.74-1.33, p=0.980]), nor for other secondary efficacy endpoints. Significantly fewer patients in the PC arm experienced drug-related grade 3/4 toxicities, 54 (43.2%) versus 71 (55.9%) for GC (p=0.045), with significantly lower rates of leukocytopenia, thrombocytopenia, and fatigue.
  
  
  CONCLUSIONS
  This study showed that in the combined population, OS of PC was superior to GC, while in the Chinese-only population, no significant difference was observed; a better safety and risk/benefit profile was found in the PC arm. A PC regimen should be considered as a standard of care in Chinese nonsquamous NSCLC patients in a first-line setting.
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangdong, China. Electronic address: syylwu@live.cn.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Lung Cancer Center, Shanghai Chest Hospital, affiliated to Shanghai JiaoTong University, Shanghai, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Oncology, Cancer Hospital of Jilin Province, Changchun, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Affiliated Cancer Institute, Shanghai, China.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Mengzhao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Oncology, 81st Hospital of the Chinese PLA, Nanjing, China.
authors.forename: Shukui
authors.initials: S
authors.lastname: Qin
authors.affiliation: Department of Oncology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: You
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Oncology, the Second Hospital of Dalian Medical University, Dalian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chest Tumor, Beijing Chest Hospital, affiliated to Capital Medical University, Beijing, China.
authors.forename: Yunzhong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Cancer Hospital affiliated to Guangxi Medical University, Nanning, China.
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Song
authors.affiliation: Asia Pacific Statistical Sciences, Lilly China Drug Development and Medical Affairs Center, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Asia Pacific Statistical Sciences, Eli Lilly Australia, Sydney, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Barraclough
authors.affiliation: Oncology, Lilly China Drug Development and Medical Affairs Center, Shanghai, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Oncology, Lilly China Drug Development and Medical Affairs Center, Shanghai, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Chi
authors.affiliation: Oncology Emerging Markets, Eli Lilly Interamérica Inc., Buenos Aires, Argentina.
authors.forename: Mauro
authors.initials: M
authors.lastname: Orlando
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D012307:Risk Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Chinese; Cisplatin; First-line chemotherapy; Gemcitabine; Non-small cell lung cancer; Nonsquamous; Pemetrexed