No standard adjuvant treatment is currently recommended in localized biliary tract cancer (BTC). Standard treatment for advanced BTC is gemcitabine combined with platinum-based chemotherapy. We aimed to assess whether GEMOX would increase relapse-free survival (RFS) while maintaining health-related quality of life (HrQoL).
We performed a multicenter, randomized phase III trial. Patients were randomized, within 3 months of R0 or R1 resection of a localized BTC, to receive either GEMOX for 12 cycles (Experimental Arm A) or surveillance (Standard Arm B). Co-primary endpoints were RFS and HrQoL. 190 patients and 126 RFS events were required to show an increase of median RFS from 18 to 30 months.
Between July 2009 and February 2014, 196 patients were included in 33 French centers. Baseline characteristics were balanced: R0 resection rate was 86% (Arm A) vs 88% (Arm B), lymph node invasion was present in 37% vs 36%. In Arm A, a median of 12 cycles was delivered. Maximal grade of adverse events was grade 3 in 58% (Arm A) vs 22% (Arm B), and grade 4 in 17% vs 9%. After a median of 46.5 months, 126 RFS events and 82 deaths were recorded. The final RFS analysis did not show any statistically significant difference between the 2 arms, with a median of 30.4 months in Arm A vs 18.5 months in Arm B (log-rank p = 0.47), Hazard Ratio (HR)=0.88 [95%CI: 0.62-1.25] (p = 0.48). The Overall Survival (OS) was not different between the 2 arms, with a median of 75.8 months [95%CI: 34.4–NE] in Arm A vs 50.8 months [95%CI: 38.0–NE] in Arm B (log-rank p = 0.74), HR = 1.08 [95%CI: 0.70-1.66] (p = 0.74). 24-months, 48-months and 72-months OS were 69%, 51% and 51% in Arm A vs 76%, 52% and 48% in Arm B, respectively. No benefit of adjuvant chemotherapy was seen in any subgroup analyses of RFS or OS.
Final RFS and first OS analysis confirmed the lack of benefit from adjuvant GEMOX in the PRODIGE 12 study. Combined analysis with other adjuvant trials is warranted.
Clinical trial identification
Legal entity responsible for the study
French Ministry of Health - PHRC-2008; Ligue Contre le Cancer, France
All authors have declared no conflicts of interest.