title: Progression-free survival as a surrogate endpoint for overall survival in patients with third-line or later-line chemotherapy for advanced gastric cancer.
abstract: BACKGROUND
  The correlation between overall survival (OS) and progression-free survival (PFS) has been evaluated in patients with metastatic or advanced gastric cancer who have received first-line and/or second-line chemotherapy. However, no corresponding analysis has been done for patients who have undergone third-line or later-line chemotherapy.
  
  
  METHODS
  A total of 303 patients from the Phase II/III studies of apatinib were pooled (the Phase II study as a training data set, the Phase III study as a testing data set). Landmark analyses of PFS at 2 months from randomization were performed to minimize lead time bias. The Cox proportional hazard model was used to test for the significance effect of PFS rate at 2 months in predicting OS. Additionally, the PFS/OS correlations were evaluated by the normal induced copula (National Institute for Health and Care Excellence) estimation model.
  
  
  RESULTS
  The median OS was 3.37 months (95% confidence interval 2.63-3.80) in patients who experienced progression at 2 months and 5.67 months in patients who did not (95% confidence interval 4.83-6.67; P<0.0001). Compared with patients who did not progress at 2 months, the adjusted hazard ratio for death was 3.39 (95% confidence interval 1.79-6.41; P<0.0001) for patients who experienced progression at 2 months. Moreover, the correlation of PFS/OS was 0.84 (95% confidence interval 0.74-0.90). Similar results were found in the testing data set.
  
  
  CONCLUSIONS
  These results indicate that PFS correlates strongly with OS, suggesting PFS may be a useful early endpoint for patients with advanced gastric cancer who have undergone third-line or later-line chemotherapy. These observations require prospective validation.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Liya
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Shao
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Lou
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
keywords: gastric cancer; overall survival; progression-free survival; surrogate endpoint