Progression-Free Survival as a Surrogate for Overall Survival in Advanced/Recurrent Gastric Cancer Trials: A Meta-Analysis

The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval [CI] = 0.852 to 0.854). The R 2 between treatment effects on PFS and on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were only moderately correlated, and we could not confirm the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cance

Survival after recurrence in patients with gastric cancer who receive S-1 adjuvant chemotherapy: exploratory analysis of the ACTS-GC trial

Abstract Background Some patients develop recurrence after curative resection and adjuvant chemotherapy. S-1, an oral fluoropyrimidine, is one of the standard regimens in adjuvant chemotherapy, and is also used in first-line treatment for advanced/metastatic gastric cancer. It is controversial as to whether the same treatment strategy can be applied for patients who develop recurrence after adjuvant chemotherapy and those who did not receive adjuvant chemotherapy. To investigate this issue, we compared the outcomes of patients who developed recurrences after treatment with or without adjuvant chemotherapy using the results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC). Methods Patients who had confirmed recurrence in the ACTS-GC trial were analyzed. We defined 2 independent cohorts. Cohort 1 patients were divided by whether they received adjuvant chemotherapy (adjuvant S-1 group and surgery-only group). Cohort 2 patients were divided by whether they received a regimen including S-1 (IS) or not including S-1 (NIS) after recurrence. Results A total of 375 patients experienced recurrence (160 in the adjuvant S-1 group and 215 in the surgery-only group). In cohort 1, the median time from recurrence to death (TFRD) was 11.4 months (95% confidence interval [CI], 8.4–13.9) in the adjuvant S-1 group and 11.3 months (95% CI, 9.7–13.1) in the surgery-only group (hazard ratio [HR], 1.05; 95% CI, 0.84–1.31). In cohort 2, 292 patients received chemotherapy after recurrence and were divided into the IS (n = 189) or the NIS group (n = 103). The median TFRD was 13.9 months (95% CI, 12.7–15.6) in the IS group and 8.1 months (95% CI, 6.6–9.7) in the NIS group (HR, 0.59; 95% CI, 0.45–0.76), and there was no significant interaction between the adjuvant S-1 group and surgery-only group. Conclusion Adjuvant chemotherapy with S-1 prolonged overall survival without influencing the TFRD. The same treatment strategy may be applied for patients who develop recurrence after adjuvant chemotherapy and those who did not receive adjuvant chemotherapy. Trial registration NCT00152217. First Posted on September 9, 2005

Additional file 3: of Survival after recurrence in patients with gastric cancer who receive S-1 adjuvant chemotherapy: exploratory analysis of the ACTS-GC trial

Table S1. Subgroup analysis of the time from recurrence to death in each group (detail for Fig. 4). (DOCX 51 kb

Additional file 3: of Survival after recurrence in patients with gastric cancer who receive S-1 adjuvant chemotherapy: exploratory analysis of the ACTS-GC trial

Table S1. Subgroup analysis of the time from recurrence to death in each group (detail for Fig. 4). (DOCX 51 kb