Progression-free survival as a surrogate endpoint for overall survival in patients with third-line or later-line chemotherapy for advanced gastric cancer

摘要

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.Conclusion: 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.