title: Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study.
abstract: BACKGROUND
  This randomized, open-label study compared pemetrexed versus docetaxel as second-line therapy for Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint tested non-inferiority of overall survival (OS) on the combined data from these patients and those in the global registration trial. Data from patients in the current study only (Chinese patients) were the basis for the study's secondary objectives.
  
  
  METHODS
  Patients with stage IIIB/IV disease were randomized (1:1) to receive pemetrexed (500 mg/m(2); 107 randomized; 106 treated) or docetaxel (75 mg/m(2); 104 randomized; 102 treated) on Day 1 of each 21-day cycle. Treatment continued until progressive disease, unacceptable toxicity or patient/investigator decision. All efficacy and safety data were analyzed at the pre-specified study completion; supplementary OS analyses were performed later, after additional events had been recorded.
  
  
  RESULTS
  The primary endpoint of OS noninferiority of pemetrexed to docetaxel was not met, the lower CL was <50% and P>0.025 (efficacy retained=97.9% [95% CLs: 47.1, 141.9]; P=0.0276), in the combined population (pemetrexed: n=390, docetaxel: n=392). Supplementary values were 101.3% (95% CLs: 57.9, 148.8), P=0.0186. For the secondary objectives, assessed in the population from the current study (pemetrexed: n=107, docetaxel: n=104), median OS was 11.7 and 12.2 months for the pemetrexed and docetaxel arms, respectively (HR [95% CLs]: 1.14 [0.78, 1.68], P=0.492). Supplementary values were 11.4 and 11.5 months, respectively (HR [95% CLs]: 1.02 [0.74, 1.40], P=0.926). Median PFS values were 2.8 and 3.1 months (HR [95% CLs]: 1.05 [0.75, 1.46], P=0.770) and ORR values were 9.6% and 4.1% (odds ratio [95% CLs]: 2.50 [0.76, 8.25], P=0.133) for pemetrexed and docetaxel, respectively. Pemetrexed-treated patients had significantly fewer drug-related grade 3-4 adverse events (pemetrexed: 20.8%, docetaxel: 40.2%; P=0.003). Few drug-related serious adverse events were reported (pemetrexed: 5 patients, docetaxel: 8 patients).
  
  
  CONCLUSIONS
  The comparable efficacy and superior tolerability of pemetrexed compared with docetaxel in this study supports the use of single-agent, second-line pemetrexed for advanced non-squamous NSCLC in Chinese patients. ClinicalTrials.gov: NCT00391274.
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China. suny@cae.cn
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: Y-L
authors.initials: YL
authors.lastname: Wu
authors.forename: C-C
authors.initials: CC
authors.lastname: Zhou
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: X-Y
authors.initials: XY
authors.lastname: Liu
authors.forename: S-Y
authors.initials: SY
authors.lastname: Yu
authors.forename: G-L
authors.initials: GL
authors.lastname: Jiang
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.forename: S-K
authors.initials: SK
authors.lastname: Qin
authors.forename: S-L
authors.initials: SL
authors.lastname: Ma
authors.forename: L
authors.initials: L
authors.lastname: Han
authors.forename: M
authors.initials: M
authors.lastname: Quinlivan
authors.forename: M
authors.initials: M
authors.lastname: Orlando
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D002681:China; D016001:Confidence Intervals; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000068437:Pemetrexed; D016016:Proportional Hazards Models; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine