Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial.

Abstract

225 Background: No standard post-surgery adjuvant treatment is currently recommended in localized biliary tract cancer (BTC). Gemcitabine combined with platinum is the standard chemotherapy for advanced BTC. The aim of this phase III randomized trial was 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 (intra-hepatic, perihilar, extra-hepatic cholangiocarcinoma or gallbladder cancer), to receive either GEMOX 85 for 12 cycles (Experimental Arm A) or surveillance (Standard Arm B). Co-primary objectives 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, with similar primary sites, R0 resection rates were 86.2% (Arm A) vs 87.9% (Arm B), lymph node invasion present in 37.2% vs 36.4%. In Arm A, a median of 12 cycles was delivered (mean: 9.3, range: 0-12). Maximal grade of adverse events were grade 3 in 57.5% vs 22.2%, and grade 4 in 17.0% vs 9.1%. During treatment one patient died in each arm. The main grade ≥ 3 adverse events in the year following inclusion were peripheral neuropathy (50.0% vs 1.1%), and neutropenia (22.3% vs 0%). Median follow-up was 44.3 months, with 54 and 64 RFS events in arms A vs B. There was no significant difference in RFS between the arms (log-rank p = 0.31), with a hazard ratio of 0.83 [95% CI: 0.58-1.19], p = 0.31 (futility boundaries were crossed). Median RFS was 30.4 [95% CI: 15.4-45.8] vs 22.0 months [95%CI: 13.6-38.3] in arms A & B respectively, and 4-years RFS was 39.3% [95%CI: 28.4%-50.0%] vs 33.2% [95%CI: 23.1-43.7%]. Global Health HrQoL scores were not different at 12 months (70.8 vs 83.3, p = 0.18) and at 24 months (75.0 vs 83.3, p = 0.50). Conclusions: Adjuvant chemotherapy in BTC with GEMOX was feasible and associated with expected toxicities and no deterioration of HrQoL. There was no significant difference in RFS between GEMOX and surveillance. Clinical trial information: NCT01313377.