Fluropyrimidine single agent or doublet chemotherapy as second line treatment in advanced biliary tract cancer

Abstract

Fluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/ gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P = .65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum-and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P = .68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting.

Patient healthcare trajectories of intrahepatic cholangiocarcinoma in France: A nationwide retrospective analysis

“… 8 In the second-line (L2) setting, the 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX) doublet recently demonstrated superiority over BSC alone in the ABC-06 phase III study, 9 but the question of the best L2 regimen is still open. 10 Finally, patients with iCCA with liver-predominant disease (50% of cases) can also be treated with locoregional therapies, including liver intra-arterial CT, selective internal radiation therapy, chemoembolization, and radiotherapy. 6 …”

Apatinib for patients with metastatic biliary tract carcinoma refractory to standard chemotherapy: results from an investigator-initiated, open-label, single-arm, exploratory phase II study

“… 10 Meanwhile, the ABC-06 trial could not prove that the FOLFOX regimen in the second-line setting was superior to fluorouracil alone, as indicated by a multicenter retrospective analysis in 525 patients with advanced BTCs. 11 …”

“…10 Meanwhile, the ABC-06 trial could not prove that the FOLFOX regimen in the second-line setting was superior to fluorouracil alone, as indicated by a multicenter retrospective analysis in 525 patients with advanced BTCs. 11 With the advent of the 'precision medicine era', targeted therapy has become a new method of drug therapy after chemotherapy in cancer management, as well as in BTCs. However, clinical studies based on the genomic information were still limited to ICC and primarily focused on isocitrate dehydrogenase (IDH) and fibroblast growth factor receptor (FGFR) targeted therapies.…”

Nonsurgical Management of Cholangiocarcinoma

“…Survival at 6 months was 50.6% vs. 35.5% and at 12 months 25.9% vs. 11.4%, all favoring the mFOLFOX arm. Retrospective analysis of two prospective multicenter cohorts showed similar overall survival with fluoropyrimidine monotherapy vs. doublets with either irinotecan or platinum chemotherapy [36]. Prospective validation of this data will be necessary to establish this as standard practice in all patients, though it provides support for fluoropyrimidine-based cytotoxic chemotherapy as second-line therapy after progression on first-line gemcitabine and cisplatin.…”