Adjuvant GEMOX for biliary tract cancer: Updated relapse-free survival and first overall survival results of the randomized PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial

Abstract

Background: 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). Methods: 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. Results: 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. Conclusions: 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.