Gemcitabine-based polychemotherapy for advanced pancreatic cancer (APC): Is it ready for prime time? A pooled analysis of 3,682 patients (pts) enrolled in 12 phase III trials
4118 Background: Since the introduction of gemcitabine (G), attempts have been made to develop G-based combination regimens to improve the dismal outcome of APC pts. Results of randomized trials, however, have been conflicting and single-agent G presently remains the standard of care for such pts. Methods: All prospective phase III trials comparing single-agent G with G-based polychemotherapy regimens (poly-G) were considered eligible. A pooled analysis was performed and event-based relative risk ratios (RR) with 95% CI were derived through both a fixed- and a random-effect model approach, exploring OS as the primary outcome and PFS and ORR as secondary outcomes. Heterogeneity between different trials was also taken into account. Results: Twelve trials involving 3682 pts were identified. The analysis was conducted considering three different subgroups: 1) overall population (3682 patients, 12 trials), 2) platinum-containing poly-G (PG) vs G (768 pts, 5 trials), and 3) fluoropyrimidine-containing poly-G (FG) vs G (1640 pts, 4 trials). As shown in the table, no significant differences in the primary outcome (OS) were observed in any of the three groups analyzed. Conversely, a significant advantage for poly-G was evident with regard to both PFS and ORR in the overall population as well as in the PG vs G subgroup, although with some heterogeneity. A heterogeneous non-significant trend towards a better PFS and ORR outcome was also observed in the FG vs G subgroup. Conclusions: Single-agent G remains the treatment of choice in APC pts. However, the addition of platinum compounds to G appears to significantly improve PFS and ORR, possibly justifying the use of platinum-based poly-G in younger and fit patients. [Table: see text] No significant financial relationships to disclose.