Meta-analysis of randomised trials comparing gemcitabine-based doublets versus gemcitabine alone in patients with advanced and metastatic pancreatic cancer

Objective: To evaluate the impact on overall survival at 6, 12 and 18 months of gemcitabine-based doublets compared with gemcitabine alone in patients with advanced and metastatic pancreatic cancer. Methods: We conducted a systematic review and meta-analysis of published data on the use of gemcitabine-based doublets compared with gemcitabine alone in chemotherapy-naive patients with advanced and metastatic pancreatic cancer treated in randomised controlled phase II-III trials with overall survival as the principal or secondary endpoint. To this end, a literature search was performed using Cochrane methodology. The relative risks with 95% confidence intervals were estimated based on adjusted number of deaths and patients at risk according to the extent of follow-up and censoring. Twenty-three randomised clinical trials including 5886 patients met the inclusion criteria. In these trials, 2932 patients were randomly assigned to receive gemcitabine-based doublets and 2954 patients to receive gemcitabine alone. Results: Gemcitabine-based doublets were associated with small but significant reductions in the risk of death at 6, 12 and 18 months of 8% (95% CI 3, 13), 4% (95% CI 2, 7) and 3% (95% CI 1, 5), respectively (p < 0.005 for all timepoints). No heterogeneity between studies was observed. Subgroup analyses showed an overall survival benefit for gemcitabine-based doublets in clinical trials testing the same planned dose intensity of gemcitabine in comparative arms, using platinum salt-based protocols and with survival as the primary endpoint. Conclusion: This meta-analysis of data obtained from randomised controlled phase II-III trials of patients with advanced pancreatic cancer showed a small but significant improvement in overall survival for patients receiving gemcitabine-based doublets compared with gemcitabine alone.