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

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. What's new? Advanced biliary tract carcinoma is usually diagnosed at an advanced stage, and requires first‐line chemotherapy. For those patients who go on to second‐line chemotherapy, most receive fluoropyrimidine (FP) alone or in combination. Here, the authors compared overall survival between patients given a second‐line treatment of FP monotherapy versus those given FP plus either irinotecan or platinum. They stratified patients by therapy regimen and by ECOG performance status, which is considered the best prognostic factor for second‐line treatment. They found that overall survival was comparable, whether patients received FP alone or in combination, even after controlling for performance status.